When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

An endoscopic severity score can achieve a higher specificity in predicting the need for selective immunosuppressive therapy among immune-mediated colitis patients than clinical symptom grading alone, according to new research presented at the annual meeting of the American College of Gastroenterology.

An endoscopy score cutoff of 4 or higher had a specificity of 82.8% across all colitis grades, and a cutoff of 5 or higher had a specificity of 87.6%, said Yinghong Wang, MD, PhD, a gastroenterologist at the University of Texas MD Anderson Cancer Center, Houston.

Immune-mediated colitis (IMC) is a common immune-related adverse event associated with immune checkpoint inhibitors. Dr. Wang and colleagues previously reported on endoscopic presentations of IMC, including severe inflammation with deep ulcerated mucosa; moderate to severe inflammation with diffuse erythema, superficial ulcers, exudate, and loss of vasculature; and mild inflammation with patchy erythema, aphtha, edema, or normal mucosa associated with histological inflammation.

An endoscopic severity score can achieve a higher specificity in predicting the need for selective immunosuppressive therapy among immune-mediated colitis patients than clinical symptom grading alone, according to new research presented at the annual meeting of the American College of Gastroenterology.

An endoscopy score cutoff of 4 or higher had a specificity of 82.8% across all colitis grades, and a cutoff of 5 or higher had a specificity of 87.6%, said Yinghong Wang, MD, PhD, a gastroenterologist at the University of Texas MD Anderson Cancer Center, Houston.

Immune-mediated colitis (IMC) is a common immune-related adverse event associated with immune checkpoint inhibitors. Dr. Wang and colleagues previously reported on endoscopic presentations of IMC, including severe inflammation with deep ulcerated mucosa; moderate to severe inflammation with diffuse erythema, superficial ulcers, exudate, and loss of vasculature; and mild inflammation with patchy erythema, aphtha, edema, or normal mucosa associated with histological inflammation.

An endoscopic severity score can achieve a higher specificity in predicting the need for selective immunosuppressive therapy among immune-mediated colitis patients than clinical symptom grading alone, according to new research presented at the annual meeting of the American College of Gastroenterology.

An endoscopy score cutoff of 4 or higher had a specificity of 82.8% across all colitis grades, and a cutoff of 5 or higher had a specificity of 87.6%, said Yinghong Wang, MD, PhD, a gastroenterologist at the University of Texas MD Anderson Cancer Center, Houston.

Immune-mediated colitis (IMC) is a common immune-related adverse event associated with immune checkpoint inhibitors. Dr. Wang and colleagues previously reported on endoscopic presentations of IMC, including severe inflammation with deep ulcerated mucosa; moderate to severe inflammation with diffuse erythema, superficial ulcers, exudate, and loss of vasculature; and mild inflammation with patchy erythema, aphtha, edema, or normal mucosa associated with histological inflammation.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Oral immunotherapy (OIT) for food allergy can help prevent anaphylaxis after accidental encounters with an allergen, but the treatment rarely cures the allergy, it has risks, and it requires long-term planning and shared decision-making by patients, their families, and their allergists, according to a new review.

In OIT, a patient who is allergic to a specific food consumes increasing amounts of the allergen over time to reduce their risk for allergic reaction.

“OIT is an elective, usually noncurative procedure with inherent risks that require families to function as amateur medical professionals. Preparing them for this role is essential to protect patients and ensure the long-term success of this life-changing procedure,” lead author Douglas P. Mack, MD, MSc, a pediatric allergy, asthma, and immunology specialist at McMaster University in Hamilton, Ont., and colleagues write in Clinical & Experimental Allergy.
 

From strict avoidance to desensitization

Food allergy treatment has traditionally involved avoiding accidental exposure that may lead to anaphylaxis and providing rescue medication. In recent years, OIT “has been recommended by several guidelines as a primary option,” Dr. Mack and coauthors write. And with the “approval by European and USA regulators of [peanut allergen powder] Palforzia [Aimmune Therapeutics], there are now commercial and noncommercial forms of OIT available for use in several countries.”

They advise physicians to take a proactive, educational, supportive approach to patients and their families throughout the therapy.

“Ultimately, the decision to pursue OIT or continue avoidance strategies remains the responsibility of the family and the patients,” they write. “Some families may not be prepared for the role that they have to play in actively managing their child’s food allergy treatment.”
 

Strategies to overcome OIT challenges

Reviewing the literature about OIT for food allergy, the authors suggest various strategies physicians can use to help OIT patients and their families prepare for and overcome common treatment-related challenges.

Two experts welcome the report

Rita Kachru, MD, a specialist in allergy and immunology and a codirector of the food allergy program at UCLA Health in Los Angeles, called this “an excellent report about a wonderful, individualized option in food allergy management.

“The authors did an excellent job delineating OIT terminology, outlining the goals, risks, and benefits of OIT, noting that it’s not a cure, and emphasizing the crucial importance of discussions with each family throughout the process,” Dr. Kachru, who was not involved in developing the report, told this news organization.

“I thoroughly agree with their assessment,” she added. “The more you do OIT research and clinical care, the more you realize the pitfalls, the benefits, and the importance of patient goals and family dynamics. Discussing the goals, risks, benefits, and alternatives to OIT in detail with the family is crucial so they fully understand the process.”

Basil M. Kahwash, MD, an allergy, pulmonary, and critical care medicine specialist at Vanderbilt University Medical Center in Nashville, Tenn., said that providers in the immunology community have been discussing OIT for years and that he welcomes the well-written report that summarizes the evidence.  

“It’s important to periodically summarize the evidence, as well as the consensus expert opinion about the evidence, so we may better inform our colleagues and patients,” said Dr. Kahwash, who was not involved in developing the report. “The authors are well-known experts in our field who have experience with OIT and with reviewing the evidence of food allergy.

“OIT can be a fantastic option for some patients, especially those who are very highly motivated and understand the process from start to finish. But OIT is not the best option for every child, and it’s not much of an option for adults,” he explained. “Patients need to be chosen carefully and understand the level of motivation required to safely follow through with the treatment.

“The report will hopefully affect patient care positively and allow patients to understand the limitations around OIT when they consider their candidacy for it,” he added. “In most cases, OIT patients will still need to avoid the allergen, but if a small amount accidentally gets into their food, they probably won’t have a very severe reaction to it.”

Dr. Kahwash would like to see data on patients who have seen long-term remission with OIT.

“Clearly, some patients benefit from OIT. What differentiates patients who benefit from OIT from those who do not?” he asked. “In the future, we need to consider possible biomarkers of patients who are and who aren’t good candidates for OIT.  

“Regardless of OIT’s limitations, the potential for desensitization rather than strict avoidance represents a big step in the evolution of food allergy treatment,” Dr. Kahwash noted.

No funding details were provided. Dr. Mack and three coauthors report financial relationships with Aimmune. Aimmune Therapeutics is the manufacturer of Palforzia OIT (AR101 powder provided in capsules and sachets). Most coauthors also report financial relationships with other pharmaceutical companies. The full list can be found with the original article. Dr. Kachru was an investigator in the PALISADES clinical trial of AR101. Dr. Kahwash reports no relevant financial relationships.

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

Oral immunotherapy (OIT) for food allergy can help prevent anaphylaxis after accidental encounters with an allergen, but the treatment rarely cures the allergy, it has risks, and it requires long-term planning and shared decision-making by patients, their families, and their allergists, according to a new review.

In OIT, a patient who is allergic to a specific food consumes increasing amounts of the allergen over time to reduce their risk for allergic reaction.

“OIT is an elective, usually noncurative procedure with inherent risks that require families to function as amateur medical professionals. Preparing them for this role is essential to protect patients and ensure the long-term success of this life-changing procedure,” lead author Douglas P. Mack, MD, MSc, a pediatric allergy, asthma, and immunology specialist at McMaster University in Hamilton, Ont., and colleagues write in Clinical & Experimental Allergy.
 

From strict avoidance to desensitization

Food allergy treatment has traditionally involved avoiding accidental exposure that may lead to anaphylaxis and providing rescue medication. In recent years, OIT “has been recommended by several guidelines as a primary option,” Dr. Mack and coauthors write. And with the “approval by European and USA regulators of [peanut allergen powder] Palforzia [Aimmune Therapeutics], there are now commercial and noncommercial forms of OIT available for use in several countries.”

They advise physicians to take a proactive, educational, supportive approach to patients and their families throughout the therapy.

“Ultimately, the decision to pursue OIT or continue avoidance strategies remains the responsibility of the family and the patients,” they write. “Some families may not be prepared for the role that they have to play in actively managing their child’s food allergy treatment.”
 

Strategies to overcome OIT challenges

Reviewing the literature about OIT for food allergy, the authors suggest various strategies physicians can use to help OIT patients and their families prepare for and overcome common treatment-related challenges.

Two experts welcome the report

Rita Kachru, MD, a specialist in allergy and immunology and a codirector of the food allergy program at UCLA Health in Los Angeles, called this “an excellent report about a wonderful, individualized option in food allergy management.

“The authors did an excellent job delineating OIT terminology, outlining the goals, risks, and benefits of OIT, noting that it’s not a cure, and emphasizing the crucial importance of discussions with each family throughout the process,” Dr. Kachru, who was not involved in developing the report, told this news organization.

“I thoroughly agree with their assessment,” she added. “The more you do OIT research and clinical care, the more you realize the pitfalls, the benefits, and the importance of patient goals and family dynamics. Discussing the goals, risks, benefits, and alternatives to OIT in detail with the family is crucial so they fully understand the process.”

Basil M. Kahwash, MD, an allergy, pulmonary, and critical care medicine specialist at Vanderbilt University Medical Center in Nashville, Tenn., said that providers in the immunology community have been discussing OIT for years and that he welcomes the well-written report that summarizes the evidence.  

“It’s important to periodically summarize the evidence, as well as the consensus expert opinion about the evidence, so we may better inform our colleagues and patients,” said Dr. Kahwash, who was not involved in developing the report. “The authors are well-known experts in our field who have experience with OIT and with reviewing the evidence of food allergy.

“OIT can be a fantastic option for some patients, especially those who are very highly motivated and understand the process from start to finish. But OIT is not the best option for every child, and it’s not much of an option for adults,” he explained. “Patients need to be chosen carefully and understand the level of motivation required to safely follow through with the treatment.

“The report will hopefully affect patient care positively and allow patients to understand the limitations around OIT when they consider their candidacy for it,” he added. “In most cases, OIT patients will still need to avoid the allergen, but if a small amount accidentally gets into their food, they probably won’t have a very severe reaction to it.”

Dr. Kahwash would like to see data on patients who have seen long-term remission with OIT.

“Clearly, some patients benefit from OIT. What differentiates patients who benefit from OIT from those who do not?” he asked. “In the future, we need to consider possible biomarkers of patients who are and who aren’t good candidates for OIT.  

“Regardless of OIT’s limitations, the potential for desensitization rather than strict avoidance represents a big step in the evolution of food allergy treatment,” Dr. Kahwash noted.

No funding details were provided. Dr. Mack and three coauthors report financial relationships with Aimmune. Aimmune Therapeutics is the manufacturer of Palforzia OIT (AR101 powder provided in capsules and sachets). Most coauthors also report financial relationships with other pharmaceutical companies. The full list can be found with the original article. Dr. Kachru was an investigator in the PALISADES clinical trial of AR101. Dr. Kahwash reports no relevant financial relationships.

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

Oral immunotherapy (OIT) for food allergy can help prevent anaphylaxis after accidental encounters with an allergen, but the treatment rarely cures the allergy, it has risks, and it requires long-term planning and shared decision-making by patients, their families, and their allergists, according to a new review.

In OIT, a patient who is allergic to a specific food consumes increasing amounts of the allergen over time to reduce their risk for allergic reaction.

“OIT is an elective, usually noncurative procedure with inherent risks that require families to function as amateur medical professionals. Preparing them for this role is essential to protect patients and ensure the long-term success of this life-changing procedure,” lead author Douglas P. Mack, MD, MSc, a pediatric allergy, asthma, and immunology specialist at McMaster University in Hamilton, Ont., and colleagues write in Clinical & Experimental Allergy.
 

From strict avoidance to desensitization

Food allergy treatment has traditionally involved avoiding accidental exposure that may lead to anaphylaxis and providing rescue medication. In recent years, OIT “has been recommended by several guidelines as a primary option,” Dr. Mack and coauthors write. And with the “approval by European and USA regulators of [peanut allergen powder] Palforzia [Aimmune Therapeutics], there are now commercial and noncommercial forms of OIT available for use in several countries.”

They advise physicians to take a proactive, educational, supportive approach to patients and their families throughout the therapy.

“Ultimately, the decision to pursue OIT or continue avoidance strategies remains the responsibility of the family and the patients,” they write. “Some families may not be prepared for the role that they have to play in actively managing their child’s food allergy treatment.”
 

Strategies to overcome OIT challenges

Reviewing the literature about OIT for food allergy, the authors suggest various strategies physicians can use to help OIT patients and their families prepare for and overcome common treatment-related challenges.

Two experts welcome the report

Rita Kachru, MD, a specialist in allergy and immunology and a codirector of the food allergy program at UCLA Health in Los Angeles, called this “an excellent report about a wonderful, individualized option in food allergy management.

“The authors did an excellent job delineating OIT terminology, outlining the goals, risks, and benefits of OIT, noting that it’s not a cure, and emphasizing the crucial importance of discussions with each family throughout the process,” Dr. Kachru, who was not involved in developing the report, told this news organization.

“I thoroughly agree with their assessment,” she added. “The more you do OIT research and clinical care, the more you realize the pitfalls, the benefits, and the importance of patient goals and family dynamics. Discussing the goals, risks, benefits, and alternatives to OIT in detail with the family is crucial so they fully understand the process.”

Basil M. Kahwash, MD, an allergy, pulmonary, and critical care medicine specialist at Vanderbilt University Medical Center in Nashville, Tenn., said that providers in the immunology community have been discussing OIT for years and that he welcomes the well-written report that summarizes the evidence.  

“It’s important to periodically summarize the evidence, as well as the consensus expert opinion about the evidence, so we may better inform our colleagues and patients,” said Dr. Kahwash, who was not involved in developing the report. “The authors are well-known experts in our field who have experience with OIT and with reviewing the evidence of food allergy.

“OIT can be a fantastic option for some patients, especially those who are very highly motivated and understand the process from start to finish. But OIT is not the best option for every child, and it’s not much of an option for adults,” he explained. “Patients need to be chosen carefully and understand the level of motivation required to safely follow through with the treatment.

“The report will hopefully affect patient care positively and allow patients to understand the limitations around OIT when they consider their candidacy for it,” he added. “In most cases, OIT patients will still need to avoid the allergen, but if a small amount accidentally gets into their food, they probably won’t have a very severe reaction to it.”

Dr. Kahwash would like to see data on patients who have seen long-term remission with OIT.

“Clearly, some patients benefit from OIT. What differentiates patients who benefit from OIT from those who do not?” he asked. “In the future, we need to consider possible biomarkers of patients who are and who aren’t good candidates for OIT.  

“Regardless of OIT’s limitations, the potential for desensitization rather than strict avoidance represents a big step in the evolution of food allergy treatment,” Dr. Kahwash noted.

No funding details were provided. Dr. Mack and three coauthors report financial relationships with Aimmune. Aimmune Therapeutics is the manufacturer of Palforzia OIT (AR101 powder provided in capsules and sachets). Most coauthors also report financial relationships with other pharmaceutical companies. The full list can be found with the original article. Dr. Kachru was an investigator in the PALISADES clinical trial of AR101. Dr. Kahwash reports no relevant financial relationships.

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