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FDA approves first tx for rare, deadly clotting disorder
Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.
The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.
The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.
Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.
Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.
The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.
“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”
A version of this article first appeared on Medscape.com.
Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.
The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.
The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.
Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.
Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.
The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.
“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”
A version of this article first appeared on Medscape.com.
Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.
The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.
The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.
Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.
Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.
The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.
“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”
A version of this article first appeared on Medscape.com.
Children with sickle cell disease at risk for vision loss
Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.
Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.
Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.
“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.
The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.
Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.
“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.
Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.
Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.
“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.
The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.
Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.
“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.
Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.
Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.
“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.
The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.
Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.
“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAO 2023
Pediatrician with SCD gives her young patients hope
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
A Case of Compound Heterozygous Factor V Leiden and Prothrombin G20210A Mutations With Recurrent Arterial Thromboembolism
BACKGROUND
There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.
CASE REPORT
We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.
CONCLUSIONS
Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.
BACKGROUND
There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.
CASE REPORT
We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.
CONCLUSIONS
Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.
BACKGROUND
There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.
CASE REPORT
We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.
CONCLUSIONS
Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.
Chimeric Antigen Receptor T-Cell Therapy in the Veterans Affairs Network: the Tennessee Valley Healthcare System Experience
BACKGROUND
Chimeric antigen receptor T-cell (CAR-T) therapy is a novel treatment for hematologic malignancies, with 6 FDA agents approved for commercial use. The Veterans Affairs (VA) Tennessee Valley Healthcare System (TVHS) is currently the only VA facility accredited to administer these agents and we are reporting the TVHS experience thus far.
METHODS
TVHS became an authorized treatment center for CAR-T therapy in September 2019 and performed its first CAR-T infusion in December 2019. This is a retrospective electronic chart review of all CAR-T veterans referred to TVHS from the program’s inception, December 1, 2019 through July 31, 2022 to evaluate at least one year of post infusion data. The primary objective is to evaluate the outcomes of veterans who received CAR-T therapy at TVHS including overall response rates (ORR), progression free survival (PFS), and overall survival (OS). Secondary objectives include assessment of toxicities, including rates and maximum grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
A total of 41 veterans have received CAR-T infusion at TVHS to date. Twenty-nine of these veterans have at least one year post-CAR-T infusion data and are included in this analysis. The majority of veterans were White (72%), male (93%), and were treated for diffuse large B-cell lymphoma (86%). Twenty-eight percent of veterans were under-represented minorities. Average age was 61 years with 62% being 65 years and older and five (17%) veterans being over the age of 74. Day 30 ORR was 90% (45% complete response [CR]). One-year PFS was 55.2% and 1-year OS was 65.5%. Of the 19 veterans who achieved CR by day 100, 79% remain in CR to date. CRS toxicity was observed in 66% of veterans (0% Grade 3 or higher). ICANS was observed in 27.5% of veterans (24% Grade 3 or higher). Only 5 (26%) veterans required transfer to the intensive care unit for additional monitoring.
CONCLUSIONS
CAR-T therapy has become a wellestablished practice at TVHS and is a safe and effective treatment option for veterans with aggressive lymphoid malignancies. Our outcomes are similar to that seen nationally with better access to under-represented minorities in an aging population.
BACKGROUND
Chimeric antigen receptor T-cell (CAR-T) therapy is a novel treatment for hematologic malignancies, with 6 FDA agents approved for commercial use. The Veterans Affairs (VA) Tennessee Valley Healthcare System (TVHS) is currently the only VA facility accredited to administer these agents and we are reporting the TVHS experience thus far.
METHODS
TVHS became an authorized treatment center for CAR-T therapy in September 2019 and performed its first CAR-T infusion in December 2019. This is a retrospective electronic chart review of all CAR-T veterans referred to TVHS from the program’s inception, December 1, 2019 through July 31, 2022 to evaluate at least one year of post infusion data. The primary objective is to evaluate the outcomes of veterans who received CAR-T therapy at TVHS including overall response rates (ORR), progression free survival (PFS), and overall survival (OS). Secondary objectives include assessment of toxicities, including rates and maximum grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
A total of 41 veterans have received CAR-T infusion at TVHS to date. Twenty-nine of these veterans have at least one year post-CAR-T infusion data and are included in this analysis. The majority of veterans were White (72%), male (93%), and were treated for diffuse large B-cell lymphoma (86%). Twenty-eight percent of veterans were under-represented minorities. Average age was 61 years with 62% being 65 years and older and five (17%) veterans being over the age of 74. Day 30 ORR was 90% (45% complete response [CR]). One-year PFS was 55.2% and 1-year OS was 65.5%. Of the 19 veterans who achieved CR by day 100, 79% remain in CR to date. CRS toxicity was observed in 66% of veterans (0% Grade 3 or higher). ICANS was observed in 27.5% of veterans (24% Grade 3 or higher). Only 5 (26%) veterans required transfer to the intensive care unit for additional monitoring.
CONCLUSIONS
CAR-T therapy has become a wellestablished practice at TVHS and is a safe and effective treatment option for veterans with aggressive lymphoid malignancies. Our outcomes are similar to that seen nationally with better access to under-represented minorities in an aging population.
BACKGROUND
Chimeric antigen receptor T-cell (CAR-T) therapy is a novel treatment for hematologic malignancies, with 6 FDA agents approved for commercial use. The Veterans Affairs (VA) Tennessee Valley Healthcare System (TVHS) is currently the only VA facility accredited to administer these agents and we are reporting the TVHS experience thus far.
METHODS
TVHS became an authorized treatment center for CAR-T therapy in September 2019 and performed its first CAR-T infusion in December 2019. This is a retrospective electronic chart review of all CAR-T veterans referred to TVHS from the program’s inception, December 1, 2019 through July 31, 2022 to evaluate at least one year of post infusion data. The primary objective is to evaluate the outcomes of veterans who received CAR-T therapy at TVHS including overall response rates (ORR), progression free survival (PFS), and overall survival (OS). Secondary objectives include assessment of toxicities, including rates and maximum grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
A total of 41 veterans have received CAR-T infusion at TVHS to date. Twenty-nine of these veterans have at least one year post-CAR-T infusion data and are included in this analysis. The majority of veterans were White (72%), male (93%), and were treated for diffuse large B-cell lymphoma (86%). Twenty-eight percent of veterans were under-represented minorities. Average age was 61 years with 62% being 65 years and older and five (17%) veterans being over the age of 74. Day 30 ORR was 90% (45% complete response [CR]). One-year PFS was 55.2% and 1-year OS was 65.5%. Of the 19 veterans who achieved CR by day 100, 79% remain in CR to date. CRS toxicity was observed in 66% of veterans (0% Grade 3 or higher). ICANS was observed in 27.5% of veterans (24% Grade 3 or higher). Only 5 (26%) veterans required transfer to the intensive care unit for additional monitoring.
CONCLUSIONS
CAR-T therapy has become a wellestablished practice at TVHS and is a safe and effective treatment option for veterans with aggressive lymphoid malignancies. Our outcomes are similar to that seen nationally with better access to under-represented minorities in an aging population.
Successful Treatment With Oral Steroids of Autoimmune Hemolytic Anemia Associated With Kikuchi-Fujimoto Disease and Systemic Lupus Erythematosus
INTRODUCTION
We present an unusual case of autoimmune hemolytic anemia (AIHA) associated with Kikuchi-Fujimoto Disease (KFD) and systemic lupus erythematosus (SLE) that resolved with steroid therapy.
CASE PRESENTATION
A 25-year-old female with no medical history presented with 6 weeks of high fevers, syncope, and 10-lb weight loss. Exam revealed generalized lymphadenopathy (LAD) and tiny malar papules. Labs showed IgG and IgM Coombs-positivity, hemoglobin of 5 g/dL, hyperbilirubinemia, low haptoglobin, LDH >2000 IU/L, thrombocytopenia, and leukopenia. Cryoglobulins were absent. Hemophagocytic lymphohistiocytosis (HLH) markers showed ferritin of 18,000 ng/mL, moderately elevated soluble IL-2 receptor, negative CD107, minimally elevated CXCL9, borderline transaminitis, and high-normal triglycerides. ANA was 1:1280, speckled, with high anti-RNP, high anti-Smith, and negative anti-dsDNA antibodies. CT confirmed LAD without organomegaly. A 4cm excised node reviewed at 2 institutions showed necrotizing lymphadenitis without granulomas, consistent with KFD. Flow cytometry and gene rearrangement assay showed no monoclonality. Bone marrow biopsy demonstrated erythroid hyperplasia, normal flow cytometry, and no hemophagocytosis. Infectious workup was unremarkable. Treatment was initiated with 50mg prednisone daily, weaned off over 5 months. 2 months post-initiation, the fevers resolved, hemoglobin increased, and LDH normalized. 3 months later, rheumatology service diagnosed SLE based on 2019 ACR/EULAR Criteria and initiated hydroxychloroquine. 9 months later, patient remains without recurrence.
DISCUSSION
KFD presents subacutely with LAD, fever, weight loss, and varying skin findings, often self-resolving. Diagnosis requires lymph node biopsy. Etiology is unclear, with infectious, neoplastic, and autoimmune mechanisms implicated. Studies suggest up to 15% of patients have SLE.
CONCLUSIONS
This case is a rare combination of AIHA, KFD, and SLE successfully treated with steroids and, later, hydroxychloroquine. It calls for vigilance for KFD in patients with LAD and AIHA. A successful treatment strategy could include highdose steroids. The presentation may mimic lymphoma and HLH, which must be ruled out with careful pathologic and lab evaluation. To our knowledge, this is the 3rd reported case of KFD with AIHA, and 2nd case of concomitant SLE, KFD, and AIHA. The only similar patient was treated with methylprednisolone and cyclophosphamide and did not have longer-term follow-up.
INTRODUCTION
We present an unusual case of autoimmune hemolytic anemia (AIHA) associated with Kikuchi-Fujimoto Disease (KFD) and systemic lupus erythematosus (SLE) that resolved with steroid therapy.
CASE PRESENTATION
A 25-year-old female with no medical history presented with 6 weeks of high fevers, syncope, and 10-lb weight loss. Exam revealed generalized lymphadenopathy (LAD) and tiny malar papules. Labs showed IgG and IgM Coombs-positivity, hemoglobin of 5 g/dL, hyperbilirubinemia, low haptoglobin, LDH >2000 IU/L, thrombocytopenia, and leukopenia. Cryoglobulins were absent. Hemophagocytic lymphohistiocytosis (HLH) markers showed ferritin of 18,000 ng/mL, moderately elevated soluble IL-2 receptor, negative CD107, minimally elevated CXCL9, borderline transaminitis, and high-normal triglycerides. ANA was 1:1280, speckled, with high anti-RNP, high anti-Smith, and negative anti-dsDNA antibodies. CT confirmed LAD without organomegaly. A 4cm excised node reviewed at 2 institutions showed necrotizing lymphadenitis without granulomas, consistent with KFD. Flow cytometry and gene rearrangement assay showed no monoclonality. Bone marrow biopsy demonstrated erythroid hyperplasia, normal flow cytometry, and no hemophagocytosis. Infectious workup was unremarkable. Treatment was initiated with 50mg prednisone daily, weaned off over 5 months. 2 months post-initiation, the fevers resolved, hemoglobin increased, and LDH normalized. 3 months later, rheumatology service diagnosed SLE based on 2019 ACR/EULAR Criteria and initiated hydroxychloroquine. 9 months later, patient remains without recurrence.
DISCUSSION
KFD presents subacutely with LAD, fever, weight loss, and varying skin findings, often self-resolving. Diagnosis requires lymph node biopsy. Etiology is unclear, with infectious, neoplastic, and autoimmune mechanisms implicated. Studies suggest up to 15% of patients have SLE.
CONCLUSIONS
This case is a rare combination of AIHA, KFD, and SLE successfully treated with steroids and, later, hydroxychloroquine. It calls for vigilance for KFD in patients with LAD and AIHA. A successful treatment strategy could include highdose steroids. The presentation may mimic lymphoma and HLH, which must be ruled out with careful pathologic and lab evaluation. To our knowledge, this is the 3rd reported case of KFD with AIHA, and 2nd case of concomitant SLE, KFD, and AIHA. The only similar patient was treated with methylprednisolone and cyclophosphamide and did not have longer-term follow-up.
INTRODUCTION
We present an unusual case of autoimmune hemolytic anemia (AIHA) associated with Kikuchi-Fujimoto Disease (KFD) and systemic lupus erythematosus (SLE) that resolved with steroid therapy.
CASE PRESENTATION
A 25-year-old female with no medical history presented with 6 weeks of high fevers, syncope, and 10-lb weight loss. Exam revealed generalized lymphadenopathy (LAD) and tiny malar papules. Labs showed IgG and IgM Coombs-positivity, hemoglobin of 5 g/dL, hyperbilirubinemia, low haptoglobin, LDH >2000 IU/L, thrombocytopenia, and leukopenia. Cryoglobulins were absent. Hemophagocytic lymphohistiocytosis (HLH) markers showed ferritin of 18,000 ng/mL, moderately elevated soluble IL-2 receptor, negative CD107, minimally elevated CXCL9, borderline transaminitis, and high-normal triglycerides. ANA was 1:1280, speckled, with high anti-RNP, high anti-Smith, and negative anti-dsDNA antibodies. CT confirmed LAD without organomegaly. A 4cm excised node reviewed at 2 institutions showed necrotizing lymphadenitis without granulomas, consistent with KFD. Flow cytometry and gene rearrangement assay showed no monoclonality. Bone marrow biopsy demonstrated erythroid hyperplasia, normal flow cytometry, and no hemophagocytosis. Infectious workup was unremarkable. Treatment was initiated with 50mg prednisone daily, weaned off over 5 months. 2 months post-initiation, the fevers resolved, hemoglobin increased, and LDH normalized. 3 months later, rheumatology service diagnosed SLE based on 2019 ACR/EULAR Criteria and initiated hydroxychloroquine. 9 months later, patient remains without recurrence.
DISCUSSION
KFD presents subacutely with LAD, fever, weight loss, and varying skin findings, often self-resolving. Diagnosis requires lymph node biopsy. Etiology is unclear, with infectious, neoplastic, and autoimmune mechanisms implicated. Studies suggest up to 15% of patients have SLE.
CONCLUSIONS
This case is a rare combination of AIHA, KFD, and SLE successfully treated with steroids and, later, hydroxychloroquine. It calls for vigilance for KFD in patients with LAD and AIHA. A successful treatment strategy could include highdose steroids. The presentation may mimic lymphoma and HLH, which must be ruled out with careful pathologic and lab evaluation. To our knowledge, this is the 3rd reported case of KFD with AIHA, and 2nd case of concomitant SLE, KFD, and AIHA. The only similar patient was treated with methylprednisolone and cyclophosphamide and did not have longer-term follow-up.
Real-World Evidence of Safety Trends Using Rituximab-PVVR in Clinic Infusions
BACKGROUND
The safety and efficacy of biosimilars are carefully reviewed by the Food and Drug Administration (FDA) to ensure the biosimilar meets the high standards for approval. However, safety concerns from infusion nursing staff prompted a review of rituximab-PVVR and rituximab for any new trends in National VA, primary literature, and facility adverse events.
METHODS
Utilizing the VA ADERS (Veteran’s Affairs Adverse Drug Event Reporting System), data was analyzed from 01/01/21 thru 04/01/23. No clear trends were identified to support an increased reaction rate for Rituximab-PVVR or Rituximab. A total of 104 Rituximab product (both parent and biosimilar products) adverse reactions were reported nationally. Of those reported, about half 56 ADEs (54%) were specifically to Rituximab-PVVR.
RESULTS
Reviewing our facility specific VA ADERS data, Birmingham VA reported 7 ADEs. Similarly other sites reported a range of 0 to 13 Rituximab product ADEs. The total number of unique patients to receive a rituximab product in the Birmingham VA since 2021 is 106, resulting in an overall incidence rate of 6.6%.
DISCUSSION
Based on the recent publication, Safety of switching between rituximab biosimilars in onco-hematology “adverse events were similar, in terms of seriousness and frequency, to those described in the literature, providing further support to the clinical safety of biosimilars.” This prospective clinical trial published in 2021, reported grade 1 rituximab related infusion events in 7.1% of patients (n=83) which correlates closely to the reported incidence at our facility referenced above (6.6%). Our current pre-medications include acetaminophen, an antihistamine, and steroid 30 minutes prior to infusion. Although our interdisciplinary team deemed this appropriate, to improve and minimize infusion reaction symptoms, the following interventions were instituted including changing ORAL Diphenhydramine to intravenous Diphenhydramine 25mg IV and providing education to infusion nursing staff on the safety and efficacy of the rituximab and biosimilar products.
CONCLUSIONS
Following the intervention (04/07/23), 36 total unique patients received rituximab products with zero incidents reported. Although the results are limited, the data may suggest IV diphenhydramine reduces the severity of ADEs which may alter reporting or show a potential “nocebo” effect could be a factor with any rituximab infusion needing further evaluation.
BACKGROUND
The safety and efficacy of biosimilars are carefully reviewed by the Food and Drug Administration (FDA) to ensure the biosimilar meets the high standards for approval. However, safety concerns from infusion nursing staff prompted a review of rituximab-PVVR and rituximab for any new trends in National VA, primary literature, and facility adverse events.
METHODS
Utilizing the VA ADERS (Veteran’s Affairs Adverse Drug Event Reporting System), data was analyzed from 01/01/21 thru 04/01/23. No clear trends were identified to support an increased reaction rate for Rituximab-PVVR or Rituximab. A total of 104 Rituximab product (both parent and biosimilar products) adverse reactions were reported nationally. Of those reported, about half 56 ADEs (54%) were specifically to Rituximab-PVVR.
RESULTS
Reviewing our facility specific VA ADERS data, Birmingham VA reported 7 ADEs. Similarly other sites reported a range of 0 to 13 Rituximab product ADEs. The total number of unique patients to receive a rituximab product in the Birmingham VA since 2021 is 106, resulting in an overall incidence rate of 6.6%.
DISCUSSION
Based on the recent publication, Safety of switching between rituximab biosimilars in onco-hematology “adverse events were similar, in terms of seriousness and frequency, to those described in the literature, providing further support to the clinical safety of biosimilars.” This prospective clinical trial published in 2021, reported grade 1 rituximab related infusion events in 7.1% of patients (n=83) which correlates closely to the reported incidence at our facility referenced above (6.6%). Our current pre-medications include acetaminophen, an antihistamine, and steroid 30 minutes prior to infusion. Although our interdisciplinary team deemed this appropriate, to improve and minimize infusion reaction symptoms, the following interventions were instituted including changing ORAL Diphenhydramine to intravenous Diphenhydramine 25mg IV and providing education to infusion nursing staff on the safety and efficacy of the rituximab and biosimilar products.
CONCLUSIONS
Following the intervention (04/07/23), 36 total unique patients received rituximab products with zero incidents reported. Although the results are limited, the data may suggest IV diphenhydramine reduces the severity of ADEs which may alter reporting or show a potential “nocebo” effect could be a factor with any rituximab infusion needing further evaluation.
BACKGROUND
The safety and efficacy of biosimilars are carefully reviewed by the Food and Drug Administration (FDA) to ensure the biosimilar meets the high standards for approval. However, safety concerns from infusion nursing staff prompted a review of rituximab-PVVR and rituximab for any new trends in National VA, primary literature, and facility adverse events.
METHODS
Utilizing the VA ADERS (Veteran’s Affairs Adverse Drug Event Reporting System), data was analyzed from 01/01/21 thru 04/01/23. No clear trends were identified to support an increased reaction rate for Rituximab-PVVR or Rituximab. A total of 104 Rituximab product (both parent and biosimilar products) adverse reactions were reported nationally. Of those reported, about half 56 ADEs (54%) were specifically to Rituximab-PVVR.
RESULTS
Reviewing our facility specific VA ADERS data, Birmingham VA reported 7 ADEs. Similarly other sites reported a range of 0 to 13 Rituximab product ADEs. The total number of unique patients to receive a rituximab product in the Birmingham VA since 2021 is 106, resulting in an overall incidence rate of 6.6%.
DISCUSSION
Based on the recent publication, Safety of switching between rituximab biosimilars in onco-hematology “adverse events were similar, in terms of seriousness and frequency, to those described in the literature, providing further support to the clinical safety of biosimilars.” This prospective clinical trial published in 2021, reported grade 1 rituximab related infusion events in 7.1% of patients (n=83) which correlates closely to the reported incidence at our facility referenced above (6.6%). Our current pre-medications include acetaminophen, an antihistamine, and steroid 30 minutes prior to infusion. Although our interdisciplinary team deemed this appropriate, to improve and minimize infusion reaction symptoms, the following interventions were instituted including changing ORAL Diphenhydramine to intravenous Diphenhydramine 25mg IV and providing education to infusion nursing staff on the safety and efficacy of the rituximab and biosimilar products.
CONCLUSIONS
Following the intervention (04/07/23), 36 total unique patients received rituximab products with zero incidents reported. Although the results are limited, the data may suggest IV diphenhydramine reduces the severity of ADEs which may alter reporting or show a potential “nocebo” effect could be a factor with any rituximab infusion needing further evaluation.
Implementation and Evaluation of a Clinical Pharmacist Practitioner-Led Pharmacogenomics Service in a Veterans Affairs Hematology and Oncology Clinic
BACKGROUND
The Pharmacogenomic Testing for Veterans (PHASER) program provides preemptive pharmacogenomic testing for Veterans nationally. Program implementation at the Madison VA began in the hematology and oncology (hem/onc) clinics. In these clinics, PHASER test results are reviewed by the hem/onc clinical pharmacist practitioner (CPP) who provides recommendations regarding therapy via an electronic health record note. The purpose of this retrospective chart review was to assess the impact of the CPP on medication management informed by pharmacogenomics.
METHODS
A retrospective chart review was completed for all Veterans enrolled in hem/onc services and offered PHASER testing between April 1, 2022 and November 1, 2022. The number and type of interventions recommended by the hem/onc CPP, acceptance of recommended interventions, and hem/onc CPP time spent were collected for all patients who accepted and completed PHASER testing. Interventions were categorized and descriptive statistics were used to summarize data.
RESULTS
Of the 98 patients reviewed by the CPP, 75 (77%) were prescribed a medication with potential pharmacogenomic implications. At least one actionable recommendation for medication therapy adjustment was identified for 40 (53%) of those patients based on their pharmacogenomic test results. The CPP spent an average of 12 minutes per patient review (range 5 to 30 minutes) and 100% of CPP recommendations were accepted.
CONCLUSIONS
The CPP efficiently reviewed pharmacogenomic test results and made meaningful recommendations for medication therapy adjustments. CPP recommendations were highly accepted in the hem/onc setting.
BACKGROUND
The Pharmacogenomic Testing for Veterans (PHASER) program provides preemptive pharmacogenomic testing for Veterans nationally. Program implementation at the Madison VA began in the hematology and oncology (hem/onc) clinics. In these clinics, PHASER test results are reviewed by the hem/onc clinical pharmacist practitioner (CPP) who provides recommendations regarding therapy via an electronic health record note. The purpose of this retrospective chart review was to assess the impact of the CPP on medication management informed by pharmacogenomics.
METHODS
A retrospective chart review was completed for all Veterans enrolled in hem/onc services and offered PHASER testing between April 1, 2022 and November 1, 2022. The number and type of interventions recommended by the hem/onc CPP, acceptance of recommended interventions, and hem/onc CPP time spent were collected for all patients who accepted and completed PHASER testing. Interventions were categorized and descriptive statistics were used to summarize data.
RESULTS
Of the 98 patients reviewed by the CPP, 75 (77%) were prescribed a medication with potential pharmacogenomic implications. At least one actionable recommendation for medication therapy adjustment was identified for 40 (53%) of those patients based on their pharmacogenomic test results. The CPP spent an average of 12 minutes per patient review (range 5 to 30 minutes) and 100% of CPP recommendations were accepted.
CONCLUSIONS
The CPP efficiently reviewed pharmacogenomic test results and made meaningful recommendations for medication therapy adjustments. CPP recommendations were highly accepted in the hem/onc setting.
BACKGROUND
The Pharmacogenomic Testing for Veterans (PHASER) program provides preemptive pharmacogenomic testing for Veterans nationally. Program implementation at the Madison VA began in the hematology and oncology (hem/onc) clinics. In these clinics, PHASER test results are reviewed by the hem/onc clinical pharmacist practitioner (CPP) who provides recommendations regarding therapy via an electronic health record note. The purpose of this retrospective chart review was to assess the impact of the CPP on medication management informed by pharmacogenomics.
METHODS
A retrospective chart review was completed for all Veterans enrolled in hem/onc services and offered PHASER testing between April 1, 2022 and November 1, 2022. The number and type of interventions recommended by the hem/onc CPP, acceptance of recommended interventions, and hem/onc CPP time spent were collected for all patients who accepted and completed PHASER testing. Interventions were categorized and descriptive statistics were used to summarize data.
RESULTS
Of the 98 patients reviewed by the CPP, 75 (77%) were prescribed a medication with potential pharmacogenomic implications. At least one actionable recommendation for medication therapy adjustment was identified for 40 (53%) of those patients based on their pharmacogenomic test results. The CPP spent an average of 12 minutes per patient review (range 5 to 30 minutes) and 100% of CPP recommendations were accepted.
CONCLUSIONS
The CPP efficiently reviewed pharmacogenomic test results and made meaningful recommendations for medication therapy adjustments. CPP recommendations were highly accepted in the hem/onc setting.
Close to Me: Cost Savings Analysis and Improving Veteran Access
BACKGROUND
While the MISSION Act for community care has increased Veteran access to specialty services, this has caused considerable fragmentation of care and financial cost to U.S. taxpayers. The VA Salt Lake City Health Care System (VA SLCHCS) referral area spans 125,000 square miles, one of the largest geographic regions in the VA health care system. Numerous VA Community- Based Outpatient Clinics (CBOCs) have been established in central and southern Utah, eastern Nevada, and southern Idaho; however, these clinics do not currently provide specialty services.
DISCUSSION
In conjunction with the National Oncology Program’s Close to Me project team, we conducted a cost analysis to determine financial feasibility of providing low-risk oncology parenteral therapies at rural CBOCs. Based on FY22 DO Paid Claim PowerBI and Pyramid Analytics Reports, VA SLCHCS paid claims for Community Care Hematology/Oncology community services in excess of $5.7 million for 380 unique Veterans (approximately $15,060 per unique Veteran). Comparatively, Veterans received high quality oncology care through VA SLCHCS with an estimated average cost of care of $5,424 per unique Veteran. Cost of parenteral therapies was estimated via review of Community Care Paid Claims Reports for individual drug claim costs (based on Jcode), VA drug pricing data from the VA National Acquisition Center Catalog, and drug unit claims data. The unit price of VA-care and community care costs were calculated and drug cost at the VA versus non- VA was compared. By retaining or re-establishing Hematology/Oncology Veteran care within VA, we estimate cost savings of approximately $9,636 per unique Veteran.
CONCLUSIONS
By re-establishing oncology care within VA SLCHCS the facility could net a substantial cost savings while simultaneously making Veterans lives easier, reduce need for transportation to/from the main SLC VA site, decrease costs due to VA pricing contracts, lessen Veteran out-of-pocket costs, improve care coordination through use of one electronic medical record, and maintain Veteran care within VA SLCHCS. Additionally, VA SLCHCS oncology will help lead the effort to launch a system within the CBOC’s to deliver high-cost parental therapies that could benefit other medical specialties such as gastroenterology, dermatology, and rheumatology.
BACKGROUND
While the MISSION Act for community care has increased Veteran access to specialty services, this has caused considerable fragmentation of care and financial cost to U.S. taxpayers. The VA Salt Lake City Health Care System (VA SLCHCS) referral area spans 125,000 square miles, one of the largest geographic regions in the VA health care system. Numerous VA Community- Based Outpatient Clinics (CBOCs) have been established in central and southern Utah, eastern Nevada, and southern Idaho; however, these clinics do not currently provide specialty services.
DISCUSSION
In conjunction with the National Oncology Program’s Close to Me project team, we conducted a cost analysis to determine financial feasibility of providing low-risk oncology parenteral therapies at rural CBOCs. Based on FY22 DO Paid Claim PowerBI and Pyramid Analytics Reports, VA SLCHCS paid claims for Community Care Hematology/Oncology community services in excess of $5.7 million for 380 unique Veterans (approximately $15,060 per unique Veteran). Comparatively, Veterans received high quality oncology care through VA SLCHCS with an estimated average cost of care of $5,424 per unique Veteran. Cost of parenteral therapies was estimated via review of Community Care Paid Claims Reports for individual drug claim costs (based on Jcode), VA drug pricing data from the VA National Acquisition Center Catalog, and drug unit claims data. The unit price of VA-care and community care costs were calculated and drug cost at the VA versus non- VA was compared. By retaining or re-establishing Hematology/Oncology Veteran care within VA, we estimate cost savings of approximately $9,636 per unique Veteran.
CONCLUSIONS
By re-establishing oncology care within VA SLCHCS the facility could net a substantial cost savings while simultaneously making Veterans lives easier, reduce need for transportation to/from the main SLC VA site, decrease costs due to VA pricing contracts, lessen Veteran out-of-pocket costs, improve care coordination through use of one electronic medical record, and maintain Veteran care within VA SLCHCS. Additionally, VA SLCHCS oncology will help lead the effort to launch a system within the CBOC’s to deliver high-cost parental therapies that could benefit other medical specialties such as gastroenterology, dermatology, and rheumatology.
BACKGROUND
While the MISSION Act for community care has increased Veteran access to specialty services, this has caused considerable fragmentation of care and financial cost to U.S. taxpayers. The VA Salt Lake City Health Care System (VA SLCHCS) referral area spans 125,000 square miles, one of the largest geographic regions in the VA health care system. Numerous VA Community- Based Outpatient Clinics (CBOCs) have been established in central and southern Utah, eastern Nevada, and southern Idaho; however, these clinics do not currently provide specialty services.
DISCUSSION
In conjunction with the National Oncology Program’s Close to Me project team, we conducted a cost analysis to determine financial feasibility of providing low-risk oncology parenteral therapies at rural CBOCs. Based on FY22 DO Paid Claim PowerBI and Pyramid Analytics Reports, VA SLCHCS paid claims for Community Care Hematology/Oncology community services in excess of $5.7 million for 380 unique Veterans (approximately $15,060 per unique Veteran). Comparatively, Veterans received high quality oncology care through VA SLCHCS with an estimated average cost of care of $5,424 per unique Veteran. Cost of parenteral therapies was estimated via review of Community Care Paid Claims Reports for individual drug claim costs (based on Jcode), VA drug pricing data from the VA National Acquisition Center Catalog, and drug unit claims data. The unit price of VA-care and community care costs were calculated and drug cost at the VA versus non- VA was compared. By retaining or re-establishing Hematology/Oncology Veteran care within VA, we estimate cost savings of approximately $9,636 per unique Veteran.
CONCLUSIONS
By re-establishing oncology care within VA SLCHCS the facility could net a substantial cost savings while simultaneously making Veterans lives easier, reduce need for transportation to/from the main SLC VA site, decrease costs due to VA pricing contracts, lessen Veteran out-of-pocket costs, improve care coordination through use of one electronic medical record, and maintain Veteran care within VA SLCHCS. Additionally, VA SLCHCS oncology will help lead the effort to launch a system within the CBOC’s to deliver high-cost parental therapies that could benefit other medical specialties such as gastroenterology, dermatology, and rheumatology.
Comparison of Intravenous Low Molecular Weight Iron Dextran and Intravenous Iron Sucrose to Treat Iron Deficiency Anemia: A Single Center Experience
PURPOSE
To evaluate if low molecular weight iron dextran (LMWID) is a safe and effective alternative to iron sucrose for intravenous iron administration.
BACKGROUND
In recent years, intravenous iron administration has increased due to clinical indications and rapid iron repletion. Early IV iron formulations had safety concerns that precluded widespread use. High molecular weight iron dextran was removed from the US market in 2009 due to safety concerns. Since then, several new IV formulations including LMWID and iron sucrose have been approved with a favorable benefit risk profile. While recent evidence and guidelines indicate that LMWID and other iron formulations have comparable safety profiles, no head-to-head comparisons exist. Both iron sucrose and LMWID are used for the treatment of IDA in Veterans Affairs hospitals. Iron sucrose is given 200 mg weekly for 5 weeks, while LMWID is given as a single 1-gram dose over 3 hours. We conducted a retrospective crosssectional analysis to compare the safety and efficacy of IV LMWID to IV iron sucrose.
METHODS
We identified 129 patients (LMWID: n=29, iron sucrose: n=100) who received intravenous iron from 01/01/2022 to 03/03/2023. To match the sample size, we selected every 3rd patient from the iron sucrose group (n=33). We captured data on infusion-related reactions, history of asthma/inflammatory bowel disease/> 2 drug allergies, overall and ≥ 2 g/dL hemoglobin increase, and treatment cost. Descriptive statistics were used to describe the safety and efficacy parameters. An unpaired t-test was used to calculate statistical significance of the cost.
RESULTS
We found that 82.7% of the patients who received LMWID had an increase in hemoglobin vs. 60.6% in the iron sucrose group. 48.3% of patients in LMWID had ≥ 2 hemoglobin increases vs. 27.3% in the iron sucrose group. The cost for LMWID administration was $2016.10, compared to $2315.40 for administration of IV iron sucrose cost. Two-tailed p value < 0.0001 indicating the observed difference to be statistically significant. No infusion reactions were observed in both groups.
CONCLUSIONS
In this single center analysis, IV LMWID administered provided comparable safety, and improved effectiveness, and cost-effectiveness to iron sucrose.
PURPOSE
To evaluate if low molecular weight iron dextran (LMWID) is a safe and effective alternative to iron sucrose for intravenous iron administration.
BACKGROUND
In recent years, intravenous iron administration has increased due to clinical indications and rapid iron repletion. Early IV iron formulations had safety concerns that precluded widespread use. High molecular weight iron dextran was removed from the US market in 2009 due to safety concerns. Since then, several new IV formulations including LMWID and iron sucrose have been approved with a favorable benefit risk profile. While recent evidence and guidelines indicate that LMWID and other iron formulations have comparable safety profiles, no head-to-head comparisons exist. Both iron sucrose and LMWID are used for the treatment of IDA in Veterans Affairs hospitals. Iron sucrose is given 200 mg weekly for 5 weeks, while LMWID is given as a single 1-gram dose over 3 hours. We conducted a retrospective crosssectional analysis to compare the safety and efficacy of IV LMWID to IV iron sucrose.
METHODS
We identified 129 patients (LMWID: n=29, iron sucrose: n=100) who received intravenous iron from 01/01/2022 to 03/03/2023. To match the sample size, we selected every 3rd patient from the iron sucrose group (n=33). We captured data on infusion-related reactions, history of asthma/inflammatory bowel disease/> 2 drug allergies, overall and ≥ 2 g/dL hemoglobin increase, and treatment cost. Descriptive statistics were used to describe the safety and efficacy parameters. An unpaired t-test was used to calculate statistical significance of the cost.
RESULTS
We found that 82.7% of the patients who received LMWID had an increase in hemoglobin vs. 60.6% in the iron sucrose group. 48.3% of patients in LMWID had ≥ 2 hemoglobin increases vs. 27.3% in the iron sucrose group. The cost for LMWID administration was $2016.10, compared to $2315.40 for administration of IV iron sucrose cost. Two-tailed p value < 0.0001 indicating the observed difference to be statistically significant. No infusion reactions were observed in both groups.
CONCLUSIONS
In this single center analysis, IV LMWID administered provided comparable safety, and improved effectiveness, and cost-effectiveness to iron sucrose.
PURPOSE
To evaluate if low molecular weight iron dextran (LMWID) is a safe and effective alternative to iron sucrose for intravenous iron administration.
BACKGROUND
In recent years, intravenous iron administration has increased due to clinical indications and rapid iron repletion. Early IV iron formulations had safety concerns that precluded widespread use. High molecular weight iron dextran was removed from the US market in 2009 due to safety concerns. Since then, several new IV formulations including LMWID and iron sucrose have been approved with a favorable benefit risk profile. While recent evidence and guidelines indicate that LMWID and other iron formulations have comparable safety profiles, no head-to-head comparisons exist. Both iron sucrose and LMWID are used for the treatment of IDA in Veterans Affairs hospitals. Iron sucrose is given 200 mg weekly for 5 weeks, while LMWID is given as a single 1-gram dose over 3 hours. We conducted a retrospective crosssectional analysis to compare the safety and efficacy of IV LMWID to IV iron sucrose.
METHODS
We identified 129 patients (LMWID: n=29, iron sucrose: n=100) who received intravenous iron from 01/01/2022 to 03/03/2023. To match the sample size, we selected every 3rd patient from the iron sucrose group (n=33). We captured data on infusion-related reactions, history of asthma/inflammatory bowel disease/> 2 drug allergies, overall and ≥ 2 g/dL hemoglobin increase, and treatment cost. Descriptive statistics were used to describe the safety and efficacy parameters. An unpaired t-test was used to calculate statistical significance of the cost.
RESULTS
We found that 82.7% of the patients who received LMWID had an increase in hemoglobin vs. 60.6% in the iron sucrose group. 48.3% of patients in LMWID had ≥ 2 hemoglobin increases vs. 27.3% in the iron sucrose group. The cost for LMWID administration was $2016.10, compared to $2315.40 for administration of IV iron sucrose cost. Two-tailed p value < 0.0001 indicating the observed difference to be statistically significant. No infusion reactions were observed in both groups.
CONCLUSIONS
In this single center analysis, IV LMWID administered provided comparable safety, and improved effectiveness, and cost-effectiveness to iron sucrose.