User login
VEXAS syndrome: More common, variable, and severe than expected
A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.
“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”
Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.
“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.
For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.
Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).
Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.
Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.
Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”
In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”
Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”
As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”
The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.
In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.
“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”
The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”
The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.
A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.
“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”
Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.
“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.
For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.
Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).
Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.
Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.
Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”
In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”
Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”
As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”
The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.
In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.
“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”
The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”
The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.
A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.
“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”
Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.
“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.
For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.
Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).
Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.
Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.
Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”
In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”
Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”
As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”
The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.
In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.
“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”
The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”
The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.
FROM JAMA
Study: Formula-fed extreme preemies need more iron
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
AT ASH 2022
Alloantibody registry would save lives, money
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Pricey gene therapy looks cost-effective for SCD
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Post Roe, pregnant SCD patients facing “dire” risks
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.
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.
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.
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.
FDA approves first gene therapy, betibeglogene autotemcel (Zynteglo), for beta-thalassemia
Betibeglogene autotemcel, a one-time gene therapy, represents a potential cure in which functional copies of the mutated gene are inserted into patients’ hematopoietic stem cells via a replication-defective lentivirus.
“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA press release. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”
The approval was based on phase 3 trials, in which 89% of 41 patients aged 4-34 years who received the therapy maintained normal or near-normal hemoglobin levels and didn’t need transfusions for at least a year. The patients were as young as age 4, maker Bluebird Bio said in a press release.
FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously recommended approval in June. The gene therapy had been approved in Europe, where it carried a price tag of about $1.8 million, but Bluebird pulled it from the market in 2021 because of problems with reimbursement.
“The decision to discontinue operations in Europe resulted from prolonged negotiations with European payers and challenges to achieving appropriate value recognition and market access,” the company said in a Securities and Exchange Commission filing.
The projected price in the United States is even higher: $2.1 million.
But the Institute for Clinical and Economic Review, an influential Boston-based nonprofit organization that specializes in medical cost-effectiveness analyses, concluded in June that, “given the high annual costs of standard care ... this new treatment meets commonly accepted value thresholds at an anticipated price of $2.1 million,” particularly with Bluebird’s proposal to pay back 80% of the cost if patients need a transfusion within 5 years.
The company is planning an October 2022 launch and estimates the U.S. market for betibeglogene autotemcel to be about 1,500 patients.
Adverse events in studies were “infrequent and consisted primarily of nonserious infusion-related reactions,” such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias, including thrombocytopenia, leukopenia, and neutropenia. One case of thrombocytopenia was considered serious but resolved, according to the company.
Most of the serious adverse events were related to hematopoietic stem cell collection and the busulfan conditioning regimen. Insertional oncogenesis and/or cancer have been reported with Bluebird’s other gene therapy products, but no cases have been associated with betibeglogene autotemcel.
A version of this article first appeared on Medscape.com.
Betibeglogene autotemcel, a one-time gene therapy, represents a potential cure in which functional copies of the mutated gene are inserted into patients’ hematopoietic stem cells via a replication-defective lentivirus.
“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA press release. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”
The approval was based on phase 3 trials, in which 89% of 41 patients aged 4-34 years who received the therapy maintained normal or near-normal hemoglobin levels and didn’t need transfusions for at least a year. The patients were as young as age 4, maker Bluebird Bio said in a press release.
FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously recommended approval in June. The gene therapy had been approved in Europe, where it carried a price tag of about $1.8 million, but Bluebird pulled it from the market in 2021 because of problems with reimbursement.
“The decision to discontinue operations in Europe resulted from prolonged negotiations with European payers and challenges to achieving appropriate value recognition and market access,” the company said in a Securities and Exchange Commission filing.
The projected price in the United States is even higher: $2.1 million.
But the Institute for Clinical and Economic Review, an influential Boston-based nonprofit organization that specializes in medical cost-effectiveness analyses, concluded in June that, “given the high annual costs of standard care ... this new treatment meets commonly accepted value thresholds at an anticipated price of $2.1 million,” particularly with Bluebird’s proposal to pay back 80% of the cost if patients need a transfusion within 5 years.
The company is planning an October 2022 launch and estimates the U.S. market for betibeglogene autotemcel to be about 1,500 patients.
Adverse events in studies were “infrequent and consisted primarily of nonserious infusion-related reactions,” such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias, including thrombocytopenia, leukopenia, and neutropenia. One case of thrombocytopenia was considered serious but resolved, according to the company.
Most of the serious adverse events were related to hematopoietic stem cell collection and the busulfan conditioning regimen. Insertional oncogenesis and/or cancer have been reported with Bluebird’s other gene therapy products, but no cases have been associated with betibeglogene autotemcel.
A version of this article first appeared on Medscape.com.
Betibeglogene autotemcel, a one-time gene therapy, represents a potential cure in which functional copies of the mutated gene are inserted into patients’ hematopoietic stem cells via a replication-defective lentivirus.
“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA press release. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”
The approval was based on phase 3 trials, in which 89% of 41 patients aged 4-34 years who received the therapy maintained normal or near-normal hemoglobin levels and didn’t need transfusions for at least a year. The patients were as young as age 4, maker Bluebird Bio said in a press release.
FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously recommended approval in June. The gene therapy had been approved in Europe, where it carried a price tag of about $1.8 million, but Bluebird pulled it from the market in 2021 because of problems with reimbursement.
“The decision to discontinue operations in Europe resulted from prolonged negotiations with European payers and challenges to achieving appropriate value recognition and market access,” the company said in a Securities and Exchange Commission filing.
The projected price in the United States is even higher: $2.1 million.
But the Institute for Clinical and Economic Review, an influential Boston-based nonprofit organization that specializes in medical cost-effectiveness analyses, concluded in June that, “given the high annual costs of standard care ... this new treatment meets commonly accepted value thresholds at an anticipated price of $2.1 million,” particularly with Bluebird’s proposal to pay back 80% of the cost if patients need a transfusion within 5 years.
The company is planning an October 2022 launch and estimates the U.S. market for betibeglogene autotemcel to be about 1,500 patients.
Adverse events in studies were “infrequent and consisted primarily of nonserious infusion-related reactions,” such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias, including thrombocytopenia, leukopenia, and neutropenia. One case of thrombocytopenia was considered serious but resolved, according to the company.
Most of the serious adverse events were related to hematopoietic stem cell collection and the busulfan conditioning regimen. Insertional oncogenesis and/or cancer have been reported with Bluebird’s other gene therapy products, but no cases have been associated with betibeglogene autotemcel.
A version of this article first appeared on Medscape.com.
Momelotinib hits the mark for deadly bone marrow cancer
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
FROM ASCO 2022
Anticipation key to tackling perioperative anemia
MANCHESTER, ENGLAND –
Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.
It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.
It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.”
The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.
It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.
Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.
Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.
The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.
As an example, she said there are already some excellent guidelines out there, but they are not widely read.
One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.
But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.
The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”
The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.
For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.
However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.
The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.
To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.
More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”
No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND –
Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.
It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.
It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.”
The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.
It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.
Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.
Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.
The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.
As an example, she said there are already some excellent guidelines out there, but they are not widely read.
One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.
But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.
The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”
The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.
For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.
However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.
The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.
To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.
More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”
No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND –
Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.
It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.
It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.”
The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.
It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.
Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.
Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.
The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.
As an example, she said there are already some excellent guidelines out there, but they are not widely read.
One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.
But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.
The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”
The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.
For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.
However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.
The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.
To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.
More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”
No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.
A version of this article first appeared on Medscape.com.
Rapper sings about living with sickle cell disease
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
FDA approves first drug for rare inherited anemia
The new drug, mitapivat (Pyrukynd, Agios), was approved on the basis of clinical trials that showed that it significantly improved hemolysis and anemia in patients with PK deficiency.
PK deficiency is rare. In clinical practice, its frequency is approximately 3-9 cases per 1 million people, the FDA noted. However, PK deficiency likely is misdiagnosed or undiagnosed, making it difficult to determine its frequency in the general population
PK deficiency is an inherited disorder that causes premature red blood cell destruction, leading to anemia, the agency explained in its announcement. Symptoms of PK deficiency range in severity and include fatigue, unusually pale skin, jaundice, shortness of breath, and a fast heart rate. Patients can also develop an enlarged spleen, can have too much iron in their blood from repeated blood transfusions, and can develop gallstones.
“Pyrukynd is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, MD, pediatric hematologist and director of hematology clinical research at Boston Children’s Hospital.
She was an investigator in the clinical trials that led to the approval. In a statement from the manufacturer, she added that “partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”
Clinical data
Clinical data that formed the basis of the approval came from two trials, one of which was a randomized, placebo-controlled trial, and the other a single-arm study, the FDA noted. In these studies, patients received up to 50 mg of mitapivat orally twice daily after an initial dose titration period
The randomized trial involved 80 adults with PK deficiency who were not having regular blood transfusions. They were allocated to receive either mitapivat or placebo and were followed for an average of 24 weeks. The primary endpoint was the number of patients who achieved a hemoglobin response (defined as a 1.5 g/dL or greater increase in hemoglobin concentration that was sustained at two or more scheduled assessments). At the end of the study, 40% of participants who received mitapivat had a hemoglobin response, compared with no participants who received placebo.
The single-arm study involved 27 adults with PK deficiency who were receiving regular blood transfusions. They took mitapivat for an average of 40 weeks. In this study, the primary endpoint was the reduction in transfusion burden, defined as at least a 33% reduction in the number of red blood cell units transfused during the last 24 weeks of treatment, compared with the historical transfusion burden on the individual participant (standardized to 24 weeks). The results show that 33% of participants who received mitapivat met this reduction in transfusion burden; 22% of participants did not require any transfusions over the last 24 weeks of treatment.
The most common side effects reported were decreases in estrone and estradiol in men, increased urate level, back pain, and joint stiffness. The effects of estrone and estradiol could not be reliably assessed in women because of normal changes in these hormone levels during the menstrual cycle and use of hormonal contraception.
The FDA warns of drug interactions that could necessitate dose adjustments, and also that abruptly stopping mitapivat could worsen premature red blood cell destruction.
The agency noted that this application received orphan drug designation, fast track designation, and priority review.
Agios is offering access programs aimed at reducing or eliminating patient out-of-pocket costs. Further details are on the myAgios patient support services program.
The company also noted that mitapivat is awaiting approval in the European Union. A decision is expected before the end of 2022.
A version of this article first appeared on Medscape.com.
The new drug, mitapivat (Pyrukynd, Agios), was approved on the basis of clinical trials that showed that it significantly improved hemolysis and anemia in patients with PK deficiency.
PK deficiency is rare. In clinical practice, its frequency is approximately 3-9 cases per 1 million people, the FDA noted. However, PK deficiency likely is misdiagnosed or undiagnosed, making it difficult to determine its frequency in the general population
PK deficiency is an inherited disorder that causes premature red blood cell destruction, leading to anemia, the agency explained in its announcement. Symptoms of PK deficiency range in severity and include fatigue, unusually pale skin, jaundice, shortness of breath, and a fast heart rate. Patients can also develop an enlarged spleen, can have too much iron in their blood from repeated blood transfusions, and can develop gallstones.
“Pyrukynd is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, MD, pediatric hematologist and director of hematology clinical research at Boston Children’s Hospital.
She was an investigator in the clinical trials that led to the approval. In a statement from the manufacturer, she added that “partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”
Clinical data
Clinical data that formed the basis of the approval came from two trials, one of which was a randomized, placebo-controlled trial, and the other a single-arm study, the FDA noted. In these studies, patients received up to 50 mg of mitapivat orally twice daily after an initial dose titration period
The randomized trial involved 80 adults with PK deficiency who were not having regular blood transfusions. They were allocated to receive either mitapivat or placebo and were followed for an average of 24 weeks. The primary endpoint was the number of patients who achieved a hemoglobin response (defined as a 1.5 g/dL or greater increase in hemoglobin concentration that was sustained at two or more scheduled assessments). At the end of the study, 40% of participants who received mitapivat had a hemoglobin response, compared with no participants who received placebo.
The single-arm study involved 27 adults with PK deficiency who were receiving regular blood transfusions. They took mitapivat for an average of 40 weeks. In this study, the primary endpoint was the reduction in transfusion burden, defined as at least a 33% reduction in the number of red blood cell units transfused during the last 24 weeks of treatment, compared with the historical transfusion burden on the individual participant (standardized to 24 weeks). The results show that 33% of participants who received mitapivat met this reduction in transfusion burden; 22% of participants did not require any transfusions over the last 24 weeks of treatment.
The most common side effects reported were decreases in estrone and estradiol in men, increased urate level, back pain, and joint stiffness. The effects of estrone and estradiol could not be reliably assessed in women because of normal changes in these hormone levels during the menstrual cycle and use of hormonal contraception.
The FDA warns of drug interactions that could necessitate dose adjustments, and also that abruptly stopping mitapivat could worsen premature red blood cell destruction.
The agency noted that this application received orphan drug designation, fast track designation, and priority review.
Agios is offering access programs aimed at reducing or eliminating patient out-of-pocket costs. Further details are on the myAgios patient support services program.
The company also noted that mitapivat is awaiting approval in the European Union. A decision is expected before the end of 2022.
A version of this article first appeared on Medscape.com.
The new drug, mitapivat (Pyrukynd, Agios), was approved on the basis of clinical trials that showed that it significantly improved hemolysis and anemia in patients with PK deficiency.
PK deficiency is rare. In clinical practice, its frequency is approximately 3-9 cases per 1 million people, the FDA noted. However, PK deficiency likely is misdiagnosed or undiagnosed, making it difficult to determine its frequency in the general population
PK deficiency is an inherited disorder that causes premature red blood cell destruction, leading to anemia, the agency explained in its announcement. Symptoms of PK deficiency range in severity and include fatigue, unusually pale skin, jaundice, shortness of breath, and a fast heart rate. Patients can also develop an enlarged spleen, can have too much iron in their blood from repeated blood transfusions, and can develop gallstones.
“Pyrukynd is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, MD, pediatric hematologist and director of hematology clinical research at Boston Children’s Hospital.
She was an investigator in the clinical trials that led to the approval. In a statement from the manufacturer, she added that “partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”
Clinical data
Clinical data that formed the basis of the approval came from two trials, one of which was a randomized, placebo-controlled trial, and the other a single-arm study, the FDA noted. In these studies, patients received up to 50 mg of mitapivat orally twice daily after an initial dose titration period
The randomized trial involved 80 adults with PK deficiency who were not having regular blood transfusions. They were allocated to receive either mitapivat or placebo and were followed for an average of 24 weeks. The primary endpoint was the number of patients who achieved a hemoglobin response (defined as a 1.5 g/dL or greater increase in hemoglobin concentration that was sustained at two or more scheduled assessments). At the end of the study, 40% of participants who received mitapivat had a hemoglobin response, compared with no participants who received placebo.
The single-arm study involved 27 adults with PK deficiency who were receiving regular blood transfusions. They took mitapivat for an average of 40 weeks. In this study, the primary endpoint was the reduction in transfusion burden, defined as at least a 33% reduction in the number of red blood cell units transfused during the last 24 weeks of treatment, compared with the historical transfusion burden on the individual participant (standardized to 24 weeks). The results show that 33% of participants who received mitapivat met this reduction in transfusion burden; 22% of participants did not require any transfusions over the last 24 weeks of treatment.
The most common side effects reported were decreases in estrone and estradiol in men, increased urate level, back pain, and joint stiffness. The effects of estrone and estradiol could not be reliably assessed in women because of normal changes in these hormone levels during the menstrual cycle and use of hormonal contraception.
The FDA warns of drug interactions that could necessitate dose adjustments, and also that abruptly stopping mitapivat could worsen premature red blood cell destruction.
The agency noted that this application received orphan drug designation, fast track designation, and priority review.
Agios is offering access programs aimed at reducing or eliminating patient out-of-pocket costs. Further details are on the myAgios patient support services program.
The company also noted that mitapivat is awaiting approval in the European Union. A decision is expected before the end of 2022.
A version of this article first appeared on Medscape.com.