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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
Mpox: Dermatology registry data pinpoints unique signs
that frequently appeared before systemic illness and a much lower overall numbers of lesions.
“Just these two findings alone show how important it is to remain clinically vigilant as dermatologists,” Esther Freeman, MD, PhD, director of global health dermatology at Massachusetts General Hospital, Boston, said in an interview. She is the corresponding author of the study, which analyzed 101 mpox cases from 13 countries and was published online on in the Journal of the American Academy of Dermatology.
“Mpox appeared to manifest differently than in previous outbreaks with morphologic and clinical evolutions much different than previously reported in endemic and prior outbreaks,” added Dr. Freeman. “Dermatologists should continue to keep mpox on the differential as it continues to circulate at low levels in the population and is a mimicker of many other common skin diseases.”
According to the Centers for Disease Control and Prevention, as of Jan. 20, 2023, there have been 30,061 cases of mpox in the United States during the outbreak that began in 2022; 23 people died. Worldwide, the number of cases neared 85,000.
Most of the affected cases were among gay, bisexual, and other men who have sex with men. A vaccination effort began last summer, and the number of cases soon plummeted. The national daily case count in January has been in the single digits.
For the new report, dermatologists tracked cases via the American Academy of Dermatology/International League of Dermatologic Societies (AAD/ILDS) Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections Registry. The new report includes data about cases entered from Aug. 4 to Nov. 13. Of these cases, 97% were male, median age was 35 years, 62% were White, 20% were Hispanic, and 11% were Black.
Just over half (54%) of patients reported skin lesions as the first sign of disease, while others had signs such as fever (16%) and malaise (9%). “This is a sharp contrast to endemic or prior outbreaks in which a ‘flu-like’ prodrome preceded lesions,” Dr. Freeman said. “Dermatologists should be aware that patients may come in with mpox skin lesions as their only initial symptoms.”
In contrast to past outbreaks where patients may have had dozens or hundreds of lesions, 20% had only 1 lesion, while 52% had 2-5 lesions, and 20% had 6-20 lesions. “There may be only a few lesions, so index of suspicion needs to be high,” Dr. Freeman said.
According to the study, “the most common skin lesion morphologies and secondary characteristics reported included papules, vesicles/blisters, pustules, erosions/ulcers and crust/scabs.” Dr. Freeman cautioned that “lesions may not go through the ‘typical’ progression from papule to pustule. The initial lesion could even be an ulceration or a crust. For dermatologists, this means you need to have a high index of suspicion, especially if you see a new onset lesion in the groin or perianal area, though they can also start elsewhere.”
She added that “the lesion you see on exam could be a classic pustule/pseudopustule, but it might not be – it could be a small perianal erosion or ulceration. If you have any concern it could be mpox, it’s a good idea to test by PCR.”
Morbilliform rash, scarring reported
The study also highlighted 10 cases of morbilliform rash. “A morbilliform exanthem is pretty nonspecific, and usually cases of mpox have more specific features,” dermatologist and study coauthor Misha Rosenbach, MD, of the University of Pennsylvania, Philadelphia, said in an interview.
“Given the current low rates of mpox, I do not think most dermatologists need to worry about mpox when evaluating morbilliform exanthems. However, in high-risk patients or patients with other morphologies, it is worth noting that there’s a chance that this may be related.”
Emory University dermatologist Howa Yeung, MD, MSc, who wasn’t involved with the study, said in an interview that morbilliform rashes in the mouth/tongue area, mostly on days 1-5, should be considered a possible sign of mpox. “While I didn’t typically think of monkeypox virus as a cause of viral exanthems, I will now add it to my differential diagnoses.”
In the report, 13% of patients had scarring, “an outcome underemphasized in the current literature” that could have long-term emotional and mental effects, the authors noted. “Some patients, particularly immunosuppressed patients, have had very large and/or ulceronecrotic lesions,” Dr. Rosenbach said. “Their scarring can be quite significant. There is, to date, very little guidance for clinicians or patients on how to mitigate this risk and, if scarring is developing, how best to manage it.”
As for lessons from the findings, Dr. Yeung said, “dermatologists need to be aware that patients with mpox can have multiple morphologies at the same time and lesions can skip stages.” And, he pointed out, it’s clear that wound care is important to prevent scarring.
The AAD has a resource page on skin care in patients with mpox that includes information about preventing scarring. Examples of mpox rashes are available on the CDC website.
The study was supported by a grant from the International League of Dermatologic Societies and in-kind support from the American Academy of Dermatology. Dr. Freeman is a coauthor for UpToDate. Dr. Freeman and Dr. Rosenbach are members of the AAD Ad Hoc Task Force to Create Monkeypox Content. Study authors reported no other disclosures, and Dr. Yeung has no disclosures.
that frequently appeared before systemic illness and a much lower overall numbers of lesions.
“Just these two findings alone show how important it is to remain clinically vigilant as dermatologists,” Esther Freeman, MD, PhD, director of global health dermatology at Massachusetts General Hospital, Boston, said in an interview. She is the corresponding author of the study, which analyzed 101 mpox cases from 13 countries and was published online on in the Journal of the American Academy of Dermatology.
“Mpox appeared to manifest differently than in previous outbreaks with morphologic and clinical evolutions much different than previously reported in endemic and prior outbreaks,” added Dr. Freeman. “Dermatologists should continue to keep mpox on the differential as it continues to circulate at low levels in the population and is a mimicker of many other common skin diseases.”
According to the Centers for Disease Control and Prevention, as of Jan. 20, 2023, there have been 30,061 cases of mpox in the United States during the outbreak that began in 2022; 23 people died. Worldwide, the number of cases neared 85,000.
Most of the affected cases were among gay, bisexual, and other men who have sex with men. A vaccination effort began last summer, and the number of cases soon plummeted. The national daily case count in January has been in the single digits.
For the new report, dermatologists tracked cases via the American Academy of Dermatology/International League of Dermatologic Societies (AAD/ILDS) Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections Registry. The new report includes data about cases entered from Aug. 4 to Nov. 13. Of these cases, 97% were male, median age was 35 years, 62% were White, 20% were Hispanic, and 11% were Black.
Just over half (54%) of patients reported skin lesions as the first sign of disease, while others had signs such as fever (16%) and malaise (9%). “This is a sharp contrast to endemic or prior outbreaks in which a ‘flu-like’ prodrome preceded lesions,” Dr. Freeman said. “Dermatologists should be aware that patients may come in with mpox skin lesions as their only initial symptoms.”
In contrast to past outbreaks where patients may have had dozens or hundreds of lesions, 20% had only 1 lesion, while 52% had 2-5 lesions, and 20% had 6-20 lesions. “There may be only a few lesions, so index of suspicion needs to be high,” Dr. Freeman said.
According to the study, “the most common skin lesion morphologies and secondary characteristics reported included papules, vesicles/blisters, pustules, erosions/ulcers and crust/scabs.” Dr. Freeman cautioned that “lesions may not go through the ‘typical’ progression from papule to pustule. The initial lesion could even be an ulceration or a crust. For dermatologists, this means you need to have a high index of suspicion, especially if you see a new onset lesion in the groin or perianal area, though they can also start elsewhere.”
She added that “the lesion you see on exam could be a classic pustule/pseudopustule, but it might not be – it could be a small perianal erosion or ulceration. If you have any concern it could be mpox, it’s a good idea to test by PCR.”
Morbilliform rash, scarring reported
The study also highlighted 10 cases of morbilliform rash. “A morbilliform exanthem is pretty nonspecific, and usually cases of mpox have more specific features,” dermatologist and study coauthor Misha Rosenbach, MD, of the University of Pennsylvania, Philadelphia, said in an interview.
“Given the current low rates of mpox, I do not think most dermatologists need to worry about mpox when evaluating morbilliform exanthems. However, in high-risk patients or patients with other morphologies, it is worth noting that there’s a chance that this may be related.”
Emory University dermatologist Howa Yeung, MD, MSc, who wasn’t involved with the study, said in an interview that morbilliform rashes in the mouth/tongue area, mostly on days 1-5, should be considered a possible sign of mpox. “While I didn’t typically think of monkeypox virus as a cause of viral exanthems, I will now add it to my differential diagnoses.”
In the report, 13% of patients had scarring, “an outcome underemphasized in the current literature” that could have long-term emotional and mental effects, the authors noted. “Some patients, particularly immunosuppressed patients, have had very large and/or ulceronecrotic lesions,” Dr. Rosenbach said. “Their scarring can be quite significant. There is, to date, very little guidance for clinicians or patients on how to mitigate this risk and, if scarring is developing, how best to manage it.”
As for lessons from the findings, Dr. Yeung said, “dermatologists need to be aware that patients with mpox can have multiple morphologies at the same time and lesions can skip stages.” And, he pointed out, it’s clear that wound care is important to prevent scarring.
The AAD has a resource page on skin care in patients with mpox that includes information about preventing scarring. Examples of mpox rashes are available on the CDC website.
The study was supported by a grant from the International League of Dermatologic Societies and in-kind support from the American Academy of Dermatology. Dr. Freeman is a coauthor for UpToDate. Dr. Freeman and Dr. Rosenbach are members of the AAD Ad Hoc Task Force to Create Monkeypox Content. Study authors reported no other disclosures, and Dr. Yeung has no disclosures.
that frequently appeared before systemic illness and a much lower overall numbers of lesions.
“Just these two findings alone show how important it is to remain clinically vigilant as dermatologists,” Esther Freeman, MD, PhD, director of global health dermatology at Massachusetts General Hospital, Boston, said in an interview. She is the corresponding author of the study, which analyzed 101 mpox cases from 13 countries and was published online on in the Journal of the American Academy of Dermatology.
“Mpox appeared to manifest differently than in previous outbreaks with morphologic and clinical evolutions much different than previously reported in endemic and prior outbreaks,” added Dr. Freeman. “Dermatologists should continue to keep mpox on the differential as it continues to circulate at low levels in the population and is a mimicker of many other common skin diseases.”
According to the Centers for Disease Control and Prevention, as of Jan. 20, 2023, there have been 30,061 cases of mpox in the United States during the outbreak that began in 2022; 23 people died. Worldwide, the number of cases neared 85,000.
Most of the affected cases were among gay, bisexual, and other men who have sex with men. A vaccination effort began last summer, and the number of cases soon plummeted. The national daily case count in January has been in the single digits.
For the new report, dermatologists tracked cases via the American Academy of Dermatology/International League of Dermatologic Societies (AAD/ILDS) Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections Registry. The new report includes data about cases entered from Aug. 4 to Nov. 13. Of these cases, 97% were male, median age was 35 years, 62% were White, 20% were Hispanic, and 11% were Black.
Just over half (54%) of patients reported skin lesions as the first sign of disease, while others had signs such as fever (16%) and malaise (9%). “This is a sharp contrast to endemic or prior outbreaks in which a ‘flu-like’ prodrome preceded lesions,” Dr. Freeman said. “Dermatologists should be aware that patients may come in with mpox skin lesions as their only initial symptoms.”
In contrast to past outbreaks where patients may have had dozens or hundreds of lesions, 20% had only 1 lesion, while 52% had 2-5 lesions, and 20% had 6-20 lesions. “There may be only a few lesions, so index of suspicion needs to be high,” Dr. Freeman said.
According to the study, “the most common skin lesion morphologies and secondary characteristics reported included papules, vesicles/blisters, pustules, erosions/ulcers and crust/scabs.” Dr. Freeman cautioned that “lesions may not go through the ‘typical’ progression from papule to pustule. The initial lesion could even be an ulceration or a crust. For dermatologists, this means you need to have a high index of suspicion, especially if you see a new onset lesion in the groin or perianal area, though they can also start elsewhere.”
She added that “the lesion you see on exam could be a classic pustule/pseudopustule, but it might not be – it could be a small perianal erosion or ulceration. If you have any concern it could be mpox, it’s a good idea to test by PCR.”
Morbilliform rash, scarring reported
The study also highlighted 10 cases of morbilliform rash. “A morbilliform exanthem is pretty nonspecific, and usually cases of mpox have more specific features,” dermatologist and study coauthor Misha Rosenbach, MD, of the University of Pennsylvania, Philadelphia, said in an interview.
“Given the current low rates of mpox, I do not think most dermatologists need to worry about mpox when evaluating morbilliform exanthems. However, in high-risk patients or patients with other morphologies, it is worth noting that there’s a chance that this may be related.”
Emory University dermatologist Howa Yeung, MD, MSc, who wasn’t involved with the study, said in an interview that morbilliform rashes in the mouth/tongue area, mostly on days 1-5, should be considered a possible sign of mpox. “While I didn’t typically think of monkeypox virus as a cause of viral exanthems, I will now add it to my differential diagnoses.”
In the report, 13% of patients had scarring, “an outcome underemphasized in the current literature” that could have long-term emotional and mental effects, the authors noted. “Some patients, particularly immunosuppressed patients, have had very large and/or ulceronecrotic lesions,” Dr. Rosenbach said. “Their scarring can be quite significant. There is, to date, very little guidance for clinicians or patients on how to mitigate this risk and, if scarring is developing, how best to manage it.”
As for lessons from the findings, Dr. Yeung said, “dermatologists need to be aware that patients with mpox can have multiple morphologies at the same time and lesions can skip stages.” And, he pointed out, it’s clear that wound care is important to prevent scarring.
The AAD has a resource page on skin care in patients with mpox that includes information about preventing scarring. Examples of mpox rashes are available on the CDC website.
The study was supported by a grant from the International League of Dermatologic Societies and in-kind support from the American Academy of Dermatology. Dr. Freeman is a coauthor for UpToDate. Dr. Freeman and Dr. Rosenbach are members of the AAD Ad Hoc Task Force to Create Monkeypox Content. Study authors reported no other disclosures, and Dr. Yeung has no disclosures.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Off their pricey CML meds, many thrive
When imatinib (Gleevec) appeared on the market just over 2 decades ago, it revolutionized the treatment of chronic myelogenous leukemia (CML) and transformed it from a grim diagnosis into a largely treatable form of blood cancer. New generations of tyrosine kinase inhibitors (TKIs) have continued to expand options for patients, and many can look forward to normal lifespans.
But these medications cause side effects and can be expensive. Long-term data doesn’t exist for the newer therapies, so no one knows whether they can harm patients over time. None of this is particularly unusual for medications to treat chronic illness, but now there’s a twist:
“Our focus has changed because the results of treatment are so good,” hematologist-oncologist Ehab L. Atallah, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “We’re trying to get people off their medication.”
Still, research estimates that only 20% of patients with CML will be eligible for treatment discontinuation and benefit from it in the long term. As a result, the wide majority of patients will need to be on drugs indefinitely.
Gleevec: A new age dawns
In the early 1990s, before the era of TKIs, the 5-year relative survival rate from CML was just 27%, and the 10-year rate was only 9.5%, according to a 2008 report. “If someone showed up with CML, their only option was to go to a bone marrow transplant. About half survived the transplant, and half of those had significant complications from it,” Dr. Atallah said. According to him, just about everyone who didn’t get transplantation would go on to die.
Then came Gleevec, which received Food and Drug Administration approval in 2001. It ushered in the era of “targeted” cancer treatment by specifically killing CML cells, instead of relying on traditional chemotherapy’s carpet-bombing approach.
“Gleevec and other TKIs have revolutionized how CML is treated, and patients are now living normal lives,” hematologist-oncologist Catherine Lai, MD, MPH, of the University of Pennsylvania, Philadelphia, said in an interview.
Alan Fahnestock, a 68-year-old retired telecommunications specialist in north-central Washington state, is one of the fortunate patients.
He was diagnosed with CML in 2004 after he underwent a thoracic CT scan in light of his tobacco use. “My GP found something odd in my lungs and referred me to a pulmonologist, who couldn’t figure it out either. He transmitted blood samples to my eventual hematologist/oncologist,” Mr. Fahnestock said in an interview. “It’s not clear to me that anybody ever figured out what the ‘oddity’ was. It has since apparently gone away. But the oncologist ran all the tests and came up with CML.”
Mr. Fahnestock hadn’t noticed any symptoms, although “this is, perhaps, because I tend not to pay a lot of attention to such things, having abused my body fairly severely over the years and having been borderline anemic since I was a kid. I don’t really expect to feel great and am a bit of a fatalist: I just get on with things until I no longer can.”
His physician prescribed Gleevec. “I had no particularly notable side effects, and carried on with my life pretty much as if nothing had happened,” Mr. Fahnestock said. He stayed on the drug for almost 20 years.
CML rooted in chromosome swap
It’s not clear exactly what causes CML, although the Mayo Clinic says most cases are linked to an abnormal, extra-short “Philadelphia chromosome,” created when two chromosomes swap material. This happens after birth.
Mr. Fahnestock thinks he happened to develop a random mutation. He also wonders if his work stints in the former Soviet Union in Vladivostok, “where the Soviet nuclear submarine fleet was decomposing,” and in Kiev, Ukraine, “which is not all that far from Chernobyl,” may be responsible.
Most patients, like Mr. Fahnestock, are men. Males will account for about 5,190 of the cases diagnosed in 2023, according to the American Cancer Society, compared to 3,740 in females.
Mr. Fahnestock’s CML diagnosis came at a fairly young age, when he was in his 40s. The average patient is diagnosed at 64. But it’s not unusual that he experienced no apparent symptoms when the cancer was found. In fact, that’s the norm.
Most patients with the disease – which is diagnosed in about 8,900 patients in the United States each year – are asymptomatic or have mild symptoms, Dr. Lai said. Their disease is discovered when “an elevated white count is found on routine blood work,” she said.
“The other group of patients typically present with very elevated white blood cell counts and splenomegaly with symptoms of fatigue and other constitutional symptoms. When the WBC count is very high, it is important to rule out transformation to accelerated or blast phase and also rule out an acute leukemia.”
Polymerase chain reaction is an especially important test during diagnosis, Dr. Atallah said, since it provides baseline data about the cancer that can be tracked.
TKIs: Mainstay of treatment
Four drugs are FDA approved for initial treatment of CML: imatinib (Gleevec), the second-generation TKIs dasatinib (Sprycel) and the third-generation TKI nilotinib (Tasigna). The third-generation TKIs bosutinib (Bosulif) and ponatinib (Iclusig) are approved for use as first-line treatments for patients who cannot tolerate the other drugs or are resistant to them.
The first-in-class drug asciminib (Scemblix), approved by the FDA in 2021, is a third-line drug for patients who failed treatment with two other TKIs and certain patients with the T315I mutation.
Dr. Lai said that it’s crucial to avoid side effects as much as possible “since the goal is for patients to be compliant and take the pill every day and not miss doses.” In younger patients, “I typically choose a second-generation TKI as my first choice, since there is a higher likelihood of getting into a deep molecular remission more quickly. If treatment-free remission is something a patient is interested in, a second-generation TKI is more likely to make this happen.”
According to Dr. Atallah, about half of patients end up using more than one drug because their initial choices either don’t work or cause intolerable side effects. Nevertheless, Dr. Lai noted: “Overall, patients do extremely well if compliant with their medication.”
Exceptions include the noncompliant and patients with more aggressive disease, like an accelerated or a blast phase, she said. For the latter patients, “allogenic bone marrow transplant should be considered once the patient is in remission.”
In remission, consider drug omission
How should patients be monitored if they are doing well?
“In general, I tend to follow patients monthly for the first six months after starting therapy, to make sure they are tolerating it well and to help manage side effects,” Dr. Lai said. “After that, I follow once every three months, and then often space out visits depending on whether they hit their molecular milestones and how long they’re in remission.”
In certain cases, patients may be taken off medication. The most recent National Comprehensive Cancer Network guidelines for treatment of CML, published in 2021, say that “discontinuation of TKI therapy (with close monitoring) is feasible in carefully selected, consenting patients” with early stage CML who’ve reached remission, defined as deep molecular response (DMR) of at least MR 4.0 for at least 2 years.
The guidelines caution that disease recurrence appears in “approximately 40%-60% of patients who discontinue TKI therapy after achieving DMR experience recurrence within 12 months of treatment cessation, in some cases as early as one month after discontinuation of TKI therapy.”
Still, the guidelines add that “resumption of TKI therapy immediately after recurrence results in the achievement of DMR in almost all patients.”
Dr. Atallah said stopping medication can be especially helpful for patients who grapple with side effects such as fatigue, diarrhea, and muscle aches. Some patients who take the drugs fear losing their health insurance and facing sky-high drug expenses. In 2018, average daily TKI costs for patients with CML were over $350, a 2020 report found.
Many patients were prescribed hugely expensive second-line treatments rather than inexpensive generic imatinib, the report said, despite “no evidence that later-generation TKIs provide superior progression free or overall survival.”
Many patients, however, refuse to consider stopping their medication, Dr. Atallah said. More data about treatment-free remission is needed, and the 21 U.S. academic medical centers in the H. Jean Khoury Cure CML Consortium are gathering information about patient outcomes.
Mr. Fahnestock is a fan of treatment-free remission. He stopped taking Gleevec about 2 years ago on the advice of his physician after he reached undetectable levels of disease.
“It was sort of a nonevent, really, with no discernible physical effects beyond exacerbation of the osteoarthritis in my hands,” he said. According to him, it’s not clear if this effect is linked to his eliminating the medication.
“I also vaguely hoped I’d feel better, even though I’d never been able to nail down any deleterious side effects,” he said. “No such luck, as it happens.”
Blood work has indicated no resurgence of the disease, and Mr. Fahnestock continues to volunteer as a rural firefighter.
“In general, I’m apparently reasonably healthy for my age, despite my folly [in younger years], and firefighting requires me to stay in reasonable shape,” he said. “I’ve recently been made aware of minor kidney issues and prediabetes. But, hell, I’m genetically scheduled to croak within 5 years or so, so why worry?”
National survival statistics in CML vary by factors such as gender and age, as a 2021 study revealed, and men have worse outcomes. Still, there’s a good chance Mr. Fahnestock won’t need to worry about CML ever again.
Dr. Atallah disclosed research support from Novartis and Takeda and has served both of those firms and Bristol-Myers Squibb as a consultant advisor. Dr. Lai discloses tied with Bristol-Myers Squibb, Jazz, Genentech, Novartis, Abbvie, Daiichi Sankyo, Astellas, MacroGenics, Servier, and Taiho. Mr. Fahnestock has no disclosures.
When imatinib (Gleevec) appeared on the market just over 2 decades ago, it revolutionized the treatment of chronic myelogenous leukemia (CML) and transformed it from a grim diagnosis into a largely treatable form of blood cancer. New generations of tyrosine kinase inhibitors (TKIs) have continued to expand options for patients, and many can look forward to normal lifespans.
But these medications cause side effects and can be expensive. Long-term data doesn’t exist for the newer therapies, so no one knows whether they can harm patients over time. None of this is particularly unusual for medications to treat chronic illness, but now there’s a twist:
“Our focus has changed because the results of treatment are so good,” hematologist-oncologist Ehab L. Atallah, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “We’re trying to get people off their medication.”
Still, research estimates that only 20% of patients with CML will be eligible for treatment discontinuation and benefit from it in the long term. As a result, the wide majority of patients will need to be on drugs indefinitely.
Gleevec: A new age dawns
In the early 1990s, before the era of TKIs, the 5-year relative survival rate from CML was just 27%, and the 10-year rate was only 9.5%, according to a 2008 report. “If someone showed up with CML, their only option was to go to a bone marrow transplant. About half survived the transplant, and half of those had significant complications from it,” Dr. Atallah said. According to him, just about everyone who didn’t get transplantation would go on to die.
Then came Gleevec, which received Food and Drug Administration approval in 2001. It ushered in the era of “targeted” cancer treatment by specifically killing CML cells, instead of relying on traditional chemotherapy’s carpet-bombing approach.
“Gleevec and other TKIs have revolutionized how CML is treated, and patients are now living normal lives,” hematologist-oncologist Catherine Lai, MD, MPH, of the University of Pennsylvania, Philadelphia, said in an interview.
Alan Fahnestock, a 68-year-old retired telecommunications specialist in north-central Washington state, is one of the fortunate patients.
He was diagnosed with CML in 2004 after he underwent a thoracic CT scan in light of his tobacco use. “My GP found something odd in my lungs and referred me to a pulmonologist, who couldn’t figure it out either. He transmitted blood samples to my eventual hematologist/oncologist,” Mr. Fahnestock said in an interview. “It’s not clear to me that anybody ever figured out what the ‘oddity’ was. It has since apparently gone away. But the oncologist ran all the tests and came up with CML.”
Mr. Fahnestock hadn’t noticed any symptoms, although “this is, perhaps, because I tend not to pay a lot of attention to such things, having abused my body fairly severely over the years and having been borderline anemic since I was a kid. I don’t really expect to feel great and am a bit of a fatalist: I just get on with things until I no longer can.”
His physician prescribed Gleevec. “I had no particularly notable side effects, and carried on with my life pretty much as if nothing had happened,” Mr. Fahnestock said. He stayed on the drug for almost 20 years.
CML rooted in chromosome swap
It’s not clear exactly what causes CML, although the Mayo Clinic says most cases are linked to an abnormal, extra-short “Philadelphia chromosome,” created when two chromosomes swap material. This happens after birth.
Mr. Fahnestock thinks he happened to develop a random mutation. He also wonders if his work stints in the former Soviet Union in Vladivostok, “where the Soviet nuclear submarine fleet was decomposing,” and in Kiev, Ukraine, “which is not all that far from Chernobyl,” may be responsible.
Most patients, like Mr. Fahnestock, are men. Males will account for about 5,190 of the cases diagnosed in 2023, according to the American Cancer Society, compared to 3,740 in females.
Mr. Fahnestock’s CML diagnosis came at a fairly young age, when he was in his 40s. The average patient is diagnosed at 64. But it’s not unusual that he experienced no apparent symptoms when the cancer was found. In fact, that’s the norm.
Most patients with the disease – which is diagnosed in about 8,900 patients in the United States each year – are asymptomatic or have mild symptoms, Dr. Lai said. Their disease is discovered when “an elevated white count is found on routine blood work,” she said.
“The other group of patients typically present with very elevated white blood cell counts and splenomegaly with symptoms of fatigue and other constitutional symptoms. When the WBC count is very high, it is important to rule out transformation to accelerated or blast phase and also rule out an acute leukemia.”
Polymerase chain reaction is an especially important test during diagnosis, Dr. Atallah said, since it provides baseline data about the cancer that can be tracked.
TKIs: Mainstay of treatment
Four drugs are FDA approved for initial treatment of CML: imatinib (Gleevec), the second-generation TKIs dasatinib (Sprycel) and the third-generation TKI nilotinib (Tasigna). The third-generation TKIs bosutinib (Bosulif) and ponatinib (Iclusig) are approved for use as first-line treatments for patients who cannot tolerate the other drugs or are resistant to them.
The first-in-class drug asciminib (Scemblix), approved by the FDA in 2021, is a third-line drug for patients who failed treatment with two other TKIs and certain patients with the T315I mutation.
Dr. Lai said that it’s crucial to avoid side effects as much as possible “since the goal is for patients to be compliant and take the pill every day and not miss doses.” In younger patients, “I typically choose a second-generation TKI as my first choice, since there is a higher likelihood of getting into a deep molecular remission more quickly. If treatment-free remission is something a patient is interested in, a second-generation TKI is more likely to make this happen.”
According to Dr. Atallah, about half of patients end up using more than one drug because their initial choices either don’t work or cause intolerable side effects. Nevertheless, Dr. Lai noted: “Overall, patients do extremely well if compliant with their medication.”
Exceptions include the noncompliant and patients with more aggressive disease, like an accelerated or a blast phase, she said. For the latter patients, “allogenic bone marrow transplant should be considered once the patient is in remission.”
In remission, consider drug omission
How should patients be monitored if they are doing well?
“In general, I tend to follow patients monthly for the first six months after starting therapy, to make sure they are tolerating it well and to help manage side effects,” Dr. Lai said. “After that, I follow once every three months, and then often space out visits depending on whether they hit their molecular milestones and how long they’re in remission.”
In certain cases, patients may be taken off medication. The most recent National Comprehensive Cancer Network guidelines for treatment of CML, published in 2021, say that “discontinuation of TKI therapy (with close monitoring) is feasible in carefully selected, consenting patients” with early stage CML who’ve reached remission, defined as deep molecular response (DMR) of at least MR 4.0 for at least 2 years.
The guidelines caution that disease recurrence appears in “approximately 40%-60% of patients who discontinue TKI therapy after achieving DMR experience recurrence within 12 months of treatment cessation, in some cases as early as one month after discontinuation of TKI therapy.”
Still, the guidelines add that “resumption of TKI therapy immediately after recurrence results in the achievement of DMR in almost all patients.”
Dr. Atallah said stopping medication can be especially helpful for patients who grapple with side effects such as fatigue, diarrhea, and muscle aches. Some patients who take the drugs fear losing their health insurance and facing sky-high drug expenses. In 2018, average daily TKI costs for patients with CML were over $350, a 2020 report found.
Many patients were prescribed hugely expensive second-line treatments rather than inexpensive generic imatinib, the report said, despite “no evidence that later-generation TKIs provide superior progression free or overall survival.”
Many patients, however, refuse to consider stopping their medication, Dr. Atallah said. More data about treatment-free remission is needed, and the 21 U.S. academic medical centers in the H. Jean Khoury Cure CML Consortium are gathering information about patient outcomes.
Mr. Fahnestock is a fan of treatment-free remission. He stopped taking Gleevec about 2 years ago on the advice of his physician after he reached undetectable levels of disease.
“It was sort of a nonevent, really, with no discernible physical effects beyond exacerbation of the osteoarthritis in my hands,” he said. According to him, it’s not clear if this effect is linked to his eliminating the medication.
“I also vaguely hoped I’d feel better, even though I’d never been able to nail down any deleterious side effects,” he said. “No such luck, as it happens.”
Blood work has indicated no resurgence of the disease, and Mr. Fahnestock continues to volunteer as a rural firefighter.
“In general, I’m apparently reasonably healthy for my age, despite my folly [in younger years], and firefighting requires me to stay in reasonable shape,” he said. “I’ve recently been made aware of minor kidney issues and prediabetes. But, hell, I’m genetically scheduled to croak within 5 years or so, so why worry?”
National survival statistics in CML vary by factors such as gender and age, as a 2021 study revealed, and men have worse outcomes. Still, there’s a good chance Mr. Fahnestock won’t need to worry about CML ever again.
Dr. Atallah disclosed research support from Novartis and Takeda and has served both of those firms and Bristol-Myers Squibb as a consultant advisor. Dr. Lai discloses tied with Bristol-Myers Squibb, Jazz, Genentech, Novartis, Abbvie, Daiichi Sankyo, Astellas, MacroGenics, Servier, and Taiho. Mr. Fahnestock has no disclosures.
When imatinib (Gleevec) appeared on the market just over 2 decades ago, it revolutionized the treatment of chronic myelogenous leukemia (CML) and transformed it from a grim diagnosis into a largely treatable form of blood cancer. New generations of tyrosine kinase inhibitors (TKIs) have continued to expand options for patients, and many can look forward to normal lifespans.
But these medications cause side effects and can be expensive. Long-term data doesn’t exist for the newer therapies, so no one knows whether they can harm patients over time. None of this is particularly unusual for medications to treat chronic illness, but now there’s a twist:
“Our focus has changed because the results of treatment are so good,” hematologist-oncologist Ehab L. Atallah, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “We’re trying to get people off their medication.”
Still, research estimates that only 20% of patients with CML will be eligible for treatment discontinuation and benefit from it in the long term. As a result, the wide majority of patients will need to be on drugs indefinitely.
Gleevec: A new age dawns
In the early 1990s, before the era of TKIs, the 5-year relative survival rate from CML was just 27%, and the 10-year rate was only 9.5%, according to a 2008 report. “If someone showed up with CML, their only option was to go to a bone marrow transplant. About half survived the transplant, and half of those had significant complications from it,” Dr. Atallah said. According to him, just about everyone who didn’t get transplantation would go on to die.
Then came Gleevec, which received Food and Drug Administration approval in 2001. It ushered in the era of “targeted” cancer treatment by specifically killing CML cells, instead of relying on traditional chemotherapy’s carpet-bombing approach.
“Gleevec and other TKIs have revolutionized how CML is treated, and patients are now living normal lives,” hematologist-oncologist Catherine Lai, MD, MPH, of the University of Pennsylvania, Philadelphia, said in an interview.
Alan Fahnestock, a 68-year-old retired telecommunications specialist in north-central Washington state, is one of the fortunate patients.
He was diagnosed with CML in 2004 after he underwent a thoracic CT scan in light of his tobacco use. “My GP found something odd in my lungs and referred me to a pulmonologist, who couldn’t figure it out either. He transmitted blood samples to my eventual hematologist/oncologist,” Mr. Fahnestock said in an interview. “It’s not clear to me that anybody ever figured out what the ‘oddity’ was. It has since apparently gone away. But the oncologist ran all the tests and came up with CML.”
Mr. Fahnestock hadn’t noticed any symptoms, although “this is, perhaps, because I tend not to pay a lot of attention to such things, having abused my body fairly severely over the years and having been borderline anemic since I was a kid. I don’t really expect to feel great and am a bit of a fatalist: I just get on with things until I no longer can.”
His physician prescribed Gleevec. “I had no particularly notable side effects, and carried on with my life pretty much as if nothing had happened,” Mr. Fahnestock said. He stayed on the drug for almost 20 years.
CML rooted in chromosome swap
It’s not clear exactly what causes CML, although the Mayo Clinic says most cases are linked to an abnormal, extra-short “Philadelphia chromosome,” created when two chromosomes swap material. This happens after birth.
Mr. Fahnestock thinks he happened to develop a random mutation. He also wonders if his work stints in the former Soviet Union in Vladivostok, “where the Soviet nuclear submarine fleet was decomposing,” and in Kiev, Ukraine, “which is not all that far from Chernobyl,” may be responsible.
Most patients, like Mr. Fahnestock, are men. Males will account for about 5,190 of the cases diagnosed in 2023, according to the American Cancer Society, compared to 3,740 in females.
Mr. Fahnestock’s CML diagnosis came at a fairly young age, when he was in his 40s. The average patient is diagnosed at 64. But it’s not unusual that he experienced no apparent symptoms when the cancer was found. In fact, that’s the norm.
Most patients with the disease – which is diagnosed in about 8,900 patients in the United States each year – are asymptomatic or have mild symptoms, Dr. Lai said. Their disease is discovered when “an elevated white count is found on routine blood work,” she said.
“The other group of patients typically present with very elevated white blood cell counts and splenomegaly with symptoms of fatigue and other constitutional symptoms. When the WBC count is very high, it is important to rule out transformation to accelerated or blast phase and also rule out an acute leukemia.”
Polymerase chain reaction is an especially important test during diagnosis, Dr. Atallah said, since it provides baseline data about the cancer that can be tracked.
TKIs: Mainstay of treatment
Four drugs are FDA approved for initial treatment of CML: imatinib (Gleevec), the second-generation TKIs dasatinib (Sprycel) and the third-generation TKI nilotinib (Tasigna). The third-generation TKIs bosutinib (Bosulif) and ponatinib (Iclusig) are approved for use as first-line treatments for patients who cannot tolerate the other drugs or are resistant to them.
The first-in-class drug asciminib (Scemblix), approved by the FDA in 2021, is a third-line drug for patients who failed treatment with two other TKIs and certain patients with the T315I mutation.
Dr. Lai said that it’s crucial to avoid side effects as much as possible “since the goal is for patients to be compliant and take the pill every day and not miss doses.” In younger patients, “I typically choose a second-generation TKI as my first choice, since there is a higher likelihood of getting into a deep molecular remission more quickly. If treatment-free remission is something a patient is interested in, a second-generation TKI is more likely to make this happen.”
According to Dr. Atallah, about half of patients end up using more than one drug because their initial choices either don’t work or cause intolerable side effects. Nevertheless, Dr. Lai noted: “Overall, patients do extremely well if compliant with their medication.”
Exceptions include the noncompliant and patients with more aggressive disease, like an accelerated or a blast phase, she said. For the latter patients, “allogenic bone marrow transplant should be considered once the patient is in remission.”
In remission, consider drug omission
How should patients be monitored if they are doing well?
“In general, I tend to follow patients monthly for the first six months after starting therapy, to make sure they are tolerating it well and to help manage side effects,” Dr. Lai said. “After that, I follow once every three months, and then often space out visits depending on whether they hit their molecular milestones and how long they’re in remission.”
In certain cases, patients may be taken off medication. The most recent National Comprehensive Cancer Network guidelines for treatment of CML, published in 2021, say that “discontinuation of TKI therapy (with close monitoring) is feasible in carefully selected, consenting patients” with early stage CML who’ve reached remission, defined as deep molecular response (DMR) of at least MR 4.0 for at least 2 years.
The guidelines caution that disease recurrence appears in “approximately 40%-60% of patients who discontinue TKI therapy after achieving DMR experience recurrence within 12 months of treatment cessation, in some cases as early as one month after discontinuation of TKI therapy.”
Still, the guidelines add that “resumption of TKI therapy immediately after recurrence results in the achievement of DMR in almost all patients.”
Dr. Atallah said stopping medication can be especially helpful for patients who grapple with side effects such as fatigue, diarrhea, and muscle aches. Some patients who take the drugs fear losing their health insurance and facing sky-high drug expenses. In 2018, average daily TKI costs for patients with CML were over $350, a 2020 report found.
Many patients were prescribed hugely expensive second-line treatments rather than inexpensive generic imatinib, the report said, despite “no evidence that later-generation TKIs provide superior progression free or overall survival.”
Many patients, however, refuse to consider stopping their medication, Dr. Atallah said. More data about treatment-free remission is needed, and the 21 U.S. academic medical centers in the H. Jean Khoury Cure CML Consortium are gathering information about patient outcomes.
Mr. Fahnestock is a fan of treatment-free remission. He stopped taking Gleevec about 2 years ago on the advice of his physician after he reached undetectable levels of disease.
“It was sort of a nonevent, really, with no discernible physical effects beyond exacerbation of the osteoarthritis in my hands,” he said. According to him, it’s not clear if this effect is linked to his eliminating the medication.
“I also vaguely hoped I’d feel better, even though I’d never been able to nail down any deleterious side effects,” he said. “No such luck, as it happens.”
Blood work has indicated no resurgence of the disease, and Mr. Fahnestock continues to volunteer as a rural firefighter.
“In general, I’m apparently reasonably healthy for my age, despite my folly [in younger years], and firefighting requires me to stay in reasonable shape,” he said. “I’ve recently been made aware of minor kidney issues and prediabetes. But, hell, I’m genetically scheduled to croak within 5 years or so, so why worry?”
National survival statistics in CML vary by factors such as gender and age, as a 2021 study revealed, and men have worse outcomes. Still, there’s a good chance Mr. Fahnestock won’t need to worry about CML ever again.
Dr. Atallah disclosed research support from Novartis and Takeda and has served both of those firms and Bristol-Myers Squibb as a consultant advisor. Dr. Lai discloses tied with Bristol-Myers Squibb, Jazz, Genentech, Novartis, Abbvie, Daiichi Sankyo, Astellas, MacroGenics, Servier, and Taiho. Mr. Fahnestock has no disclosures.
Surgeon’s license suspension spotlights hazards, ethics of live-streaming surgeries
potentially endangering patients. The surgeon has a large social media following.
In November, the State Medical Board of Ohio temporarily suspended the license of Katherine Roxanne Grawe, MD, who practices in the wealthy Columbus suburb of Powell.
Among other accusations of misconduct, the board stated that “during some videos/live-streams you engage in dialogue to respond to viewers’ online questions while the surgical procedure remains actively ongoing.”
One patient needed emergency treatment following liposuction and was diagnosed with a perforated bowel and serious bacterial infection.
“Despite liposuction being a blind surgery that requires awareness of the tip of the cannula to avoid injury, your attention to the camera meant at those moments you were not looking at the patient or palpating the location of the tip of the cannula,” the medical board said.
Neither Dr. Grawe nor her attorney responded to requests for comment.
Dr. Grawe, known as “Dr. Roxy,” has a popular TikTok account – now set to private – with 841,600 followers and 14.6 million likes. She has another 123,000 followers on her Instagram account, also now private.
The Columbus Dispatch reported that Dr. Grawe had previously been warned to protect patient privacy on social media. The board has yet to make a final decision regarding her license.
According to Columbus TV station WSYX, she said in a TikTok video, “We show our surgeries every single day on Snapchat. Patients get to decide if they want to be part of it. And if you do, you can watch your own surgery.”
The TV station quoted former patients who described surgical complications. One said: “I went to her because, I thought, from all of her social media that she uplifted women. That she helped women empower themselves. But she didn’t.”
Dallas plastic surgeon Rod J. Rohrich, MD, who has written about social-media best practices and has 430,000 followers on Instagram, said in an interview that many surgeons have been reprimanded by state medical boards for being distracted by social media during procedures.
“It is best not to do live-streaming unless it is an educational event to demonstrate techniques and technology with full informed consent of the patient. It should be a very well-rehearsed event for education,” he said.
Nurses also have been disciplined for inappropriate posts on social media. In December 2022, an Atlanta hospital announced that four nurses were no longer on the job after they appeared in a TikTok video in scrubs and revealed their “icks” regarding obstetric care.
“My ick is when you ask me how much the baby weighs,” one worker said in the video, “and it’s still ... in your hands.”
Plastic surgeon Christian J. Vercler, MD, of the University of Michigan, Ann Arbor, who’s studied social-media guidelines for surgeons, said in an interview that plastic surgery content on TikTok has “blown up” in recent years.
“Five years or so ago, it was Snapchat where I saw a lot of inappropriate things posted by surgeons,” Dr. Vercler said in an interview. “That may still be happening on Snapchat, but I actually don’t ever use that platform anymore, and neither do my trainees.”
Dr. Vercler cautioned colleagues to consider their motivations for live-streaming surgery and to think about whether they can fully focus on the patient.
“There are many potential distractions in the OR. We get pages, phone calls, nurses asking us questions, anesthesiologists trying to talk to us. Social media is just one more thing competing for the surgeon’s attention,” he said. “Every surgeon should strive to eliminate unnecessary or unavoidable distractions, so the question becomes, ‘who is best being served by me focusing my attention on recording this operation on someone’s phone so we can post it on social media? Is it the patient?’ ”
Dr. Vercler added, “There are many, many plastic surgeons using social media as the powerful platform that it is to build their brands, to connect with potential patients, and to educate the public about what they do. I believe that most are doing this in a way that is respectful to patients and doesn’t exploit patients for the surgeon’s benefit.
“Unfortunately,” he concluded, “there are some who do see patients as merely instruments by which they can achieve fame, notoriety, and wealth.”
Dr. Rohrich and Dr. Vercler disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
potentially endangering patients. The surgeon has a large social media following.
In November, the State Medical Board of Ohio temporarily suspended the license of Katherine Roxanne Grawe, MD, who practices in the wealthy Columbus suburb of Powell.
Among other accusations of misconduct, the board stated that “during some videos/live-streams you engage in dialogue to respond to viewers’ online questions while the surgical procedure remains actively ongoing.”
One patient needed emergency treatment following liposuction and was diagnosed with a perforated bowel and serious bacterial infection.
“Despite liposuction being a blind surgery that requires awareness of the tip of the cannula to avoid injury, your attention to the camera meant at those moments you were not looking at the patient or palpating the location of the tip of the cannula,” the medical board said.
Neither Dr. Grawe nor her attorney responded to requests for comment.
Dr. Grawe, known as “Dr. Roxy,” has a popular TikTok account – now set to private – with 841,600 followers and 14.6 million likes. She has another 123,000 followers on her Instagram account, also now private.
The Columbus Dispatch reported that Dr. Grawe had previously been warned to protect patient privacy on social media. The board has yet to make a final decision regarding her license.
According to Columbus TV station WSYX, she said in a TikTok video, “We show our surgeries every single day on Snapchat. Patients get to decide if they want to be part of it. And if you do, you can watch your own surgery.”
The TV station quoted former patients who described surgical complications. One said: “I went to her because, I thought, from all of her social media that she uplifted women. That she helped women empower themselves. But she didn’t.”
Dallas plastic surgeon Rod J. Rohrich, MD, who has written about social-media best practices and has 430,000 followers on Instagram, said in an interview that many surgeons have been reprimanded by state medical boards for being distracted by social media during procedures.
“It is best not to do live-streaming unless it is an educational event to demonstrate techniques and technology with full informed consent of the patient. It should be a very well-rehearsed event for education,” he said.
Nurses also have been disciplined for inappropriate posts on social media. In December 2022, an Atlanta hospital announced that four nurses were no longer on the job after they appeared in a TikTok video in scrubs and revealed their “icks” regarding obstetric care.
“My ick is when you ask me how much the baby weighs,” one worker said in the video, “and it’s still ... in your hands.”
Plastic surgeon Christian J. Vercler, MD, of the University of Michigan, Ann Arbor, who’s studied social-media guidelines for surgeons, said in an interview that plastic surgery content on TikTok has “blown up” in recent years.
“Five years or so ago, it was Snapchat where I saw a lot of inappropriate things posted by surgeons,” Dr. Vercler said in an interview. “That may still be happening on Snapchat, but I actually don’t ever use that platform anymore, and neither do my trainees.”
Dr. Vercler cautioned colleagues to consider their motivations for live-streaming surgery and to think about whether they can fully focus on the patient.
“There are many potential distractions in the OR. We get pages, phone calls, nurses asking us questions, anesthesiologists trying to talk to us. Social media is just one more thing competing for the surgeon’s attention,” he said. “Every surgeon should strive to eliminate unnecessary or unavoidable distractions, so the question becomes, ‘who is best being served by me focusing my attention on recording this operation on someone’s phone so we can post it on social media? Is it the patient?’ ”
Dr. Vercler added, “There are many, many plastic surgeons using social media as the powerful platform that it is to build their brands, to connect with potential patients, and to educate the public about what they do. I believe that most are doing this in a way that is respectful to patients and doesn’t exploit patients for the surgeon’s benefit.
“Unfortunately,” he concluded, “there are some who do see patients as merely instruments by which they can achieve fame, notoriety, and wealth.”
Dr. Rohrich and Dr. Vercler disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
potentially endangering patients. The surgeon has a large social media following.
In November, the State Medical Board of Ohio temporarily suspended the license of Katherine Roxanne Grawe, MD, who practices in the wealthy Columbus suburb of Powell.
Among other accusations of misconduct, the board stated that “during some videos/live-streams you engage in dialogue to respond to viewers’ online questions while the surgical procedure remains actively ongoing.”
One patient needed emergency treatment following liposuction and was diagnosed with a perforated bowel and serious bacterial infection.
“Despite liposuction being a blind surgery that requires awareness of the tip of the cannula to avoid injury, your attention to the camera meant at those moments you were not looking at the patient or palpating the location of the tip of the cannula,” the medical board said.
Neither Dr. Grawe nor her attorney responded to requests for comment.
Dr. Grawe, known as “Dr. Roxy,” has a popular TikTok account – now set to private – with 841,600 followers and 14.6 million likes. She has another 123,000 followers on her Instagram account, also now private.
The Columbus Dispatch reported that Dr. Grawe had previously been warned to protect patient privacy on social media. The board has yet to make a final decision regarding her license.
According to Columbus TV station WSYX, she said in a TikTok video, “We show our surgeries every single day on Snapchat. Patients get to decide if they want to be part of it. And if you do, you can watch your own surgery.”
The TV station quoted former patients who described surgical complications. One said: “I went to her because, I thought, from all of her social media that she uplifted women. That she helped women empower themselves. But she didn’t.”
Dallas plastic surgeon Rod J. Rohrich, MD, who has written about social-media best practices and has 430,000 followers on Instagram, said in an interview that many surgeons have been reprimanded by state medical boards for being distracted by social media during procedures.
“It is best not to do live-streaming unless it is an educational event to demonstrate techniques and technology with full informed consent of the patient. It should be a very well-rehearsed event for education,” he said.
Nurses also have been disciplined for inappropriate posts on social media. In December 2022, an Atlanta hospital announced that four nurses were no longer on the job after they appeared in a TikTok video in scrubs and revealed their “icks” regarding obstetric care.
“My ick is when you ask me how much the baby weighs,” one worker said in the video, “and it’s still ... in your hands.”
Plastic surgeon Christian J. Vercler, MD, of the University of Michigan, Ann Arbor, who’s studied social-media guidelines for surgeons, said in an interview that plastic surgery content on TikTok has “blown up” in recent years.
“Five years or so ago, it was Snapchat where I saw a lot of inappropriate things posted by surgeons,” Dr. Vercler said in an interview. “That may still be happening on Snapchat, but I actually don’t ever use that platform anymore, and neither do my trainees.”
Dr. Vercler cautioned colleagues to consider their motivations for live-streaming surgery and to think about whether they can fully focus on the patient.
“There are many potential distractions in the OR. We get pages, phone calls, nurses asking us questions, anesthesiologists trying to talk to us. Social media is just one more thing competing for the surgeon’s attention,” he said. “Every surgeon should strive to eliminate unnecessary or unavoidable distractions, so the question becomes, ‘who is best being served by me focusing my attention on recording this operation on someone’s phone so we can post it on social media? Is it the patient?’ ”
Dr. Vercler added, “There are many, many plastic surgeons using social media as the powerful platform that it is to build their brands, to connect with potential patients, and to educate the public about what they do. I believe that most are doing this in a way that is respectful to patients and doesn’t exploit patients for the surgeon’s benefit.
“Unfortunately,” he concluded, “there are some who do see patients as merely instruments by which they can achieve fame, notoriety, and wealth.”
Dr. Rohrich and Dr. Vercler disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID update: ASH experts discuss thrombosis, immunity
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
AT ASH 2022
AAP offers new guidance on child exploitation and sex trafficking
In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.
“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”
The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.
As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.
Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”
Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”
Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?
Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.
- The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
- The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
- The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.
What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.
“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”
That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.
And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”
The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”
Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.
The study has no external funding. The authors report no disclosures.
In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.
“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”
The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.
As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.
Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”
Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”
Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?
Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.
- The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
- The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
- The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.
What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.
“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”
That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.
And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”
The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”
Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.
The study has no external funding. The authors report no disclosures.
In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.
“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”
The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.
As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.
Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”
Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”
Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?
Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.
- The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
- The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
- The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.
What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.
“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”
That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.
And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”
The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”
Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.
The study has no external funding. The authors report no disclosures.
FROM PEDIATRICS
Immunotherapy drug boosts survival in newly diagnosed ALL
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
AT ASH 2022
Antipsychotic shows benefit for Alzheimer’s agitation
SAN FRANCISCO – In a widely anticipated report,
Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.
“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”
Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.
In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.
Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
Three trials
All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.
Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.
The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”
The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).
In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).
In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.
The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.
The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.
Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.
University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”
But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”
What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.
Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – In a widely anticipated report,
Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.
“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”
Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.
In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.
Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
Three trials
All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.
Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.
The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”
The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).
In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).
In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.
The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.
The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.
Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.
University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”
But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”
What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.
Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – In a widely anticipated report,
Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.
“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”
Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.
In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.
Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
Three trials
All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.
Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.
The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”
The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).
In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).
In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.
The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.
The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.
Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.
University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”
But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”
What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.
Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
A version of this article first appeared on Medscape.com.
AT CTAD 2022
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
ITP: Biologic beat placebo, but few patients improved
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
AT ASH 2022