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CAR T-cell therapy: Moving from cost to value
Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.
“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.
In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
Price tag pressure
During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.
The “list price” for tisagenlecleucel is $475,000, and the potential patient pool is in the hundreds. The price for axicabtagene ciloleucel is $373,000, with a potential market in the thousands. Taking this into account, the global CAR T market is estimated at about $72 million and is projected to expand to nearly $3.5 billion in the next decade, said Dr. Maziarz, who is also chair of the Value and Health Economics Interest Group of the American Society for Blood and Marrow Transplantation.
The market for adoptive cell therapy overall – including transplant, CAR T, natural killer cells, and cell vaccines – is projected by some individuals to be worth $30 billion by 2030, he added, noting, for the sake of comparison, that the total estimated U.S. expenditure for all cancer care in the United States in 2010 was $125 billion.
At the heart of the issue of cost is the matter of value, he said.
“You can talk about price, and you can talk about cost, but … what we want to do with our dollars is buy value – and quality and value are very hard to measure,” he said, noting that he expects public and governmental backlash, as was seen with prior high-cost treatments such as Sovaldi for hepatitis C and Glybera for lipoprotein lipase deficiency.
Value-based payment is a recurrent theme in medicine, and these treatments came under intense scrutiny for their high costs. Sovaldi, for example, costs approximately $90,000 for a treatment course. That sounds like a lot of money, but it cures the disease and can prevent long-term complications, Dr. Maziarz said. Still, it received a lot of negative press, and the backlash was severe.
“People do respond to price,” he said, noting that he predicts the same for CAR T-cell therapies.
The costs of CAR T-cell therapy, particularly when taking into consideration the costs that hospitals will incur given the lymphodepletion that patients experience and the after-care required, will likely exceed those of most stem cell transplants and could easily reach the $1 million-plus estimates, Helen Heslop, MD, professor of medicine and pediatrics and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston, said in an interview.
Aside from the research and development costs, these treatments also cost more to make than any others previously made, according to Carl H. June, MD, the Richard W. Vague Professor In Immunotherapy at the University of Pennsylvania, Philadelphia, and a pioneer in CAR T-cell research.
Dr. June predicted that costs will be forced down over time because of process improvements and competition. “What’s unknown is the time span on how long it will take,” he said in an interview.
Groups like the United Kingdom’s National Institute for Health and Care Excellence (NICE) are already looking at value-based approaches to providing CAR T-cell therapy, Dr. Heslop said.
“I think there will need to be a lot more comparative effectiveness analyses done,” she said. “I know my institution started to look at the cost in a child with ALL once they relapse, and when you look at all the downstream cost, even though [CAR T-cell therapy] sounds very expensive, as a one-time therapy versus much longer treatment, it may actually be value based,” she said.
When it comes to improving access, one of the approaches being studied is the use of universal cell banks as opposed to autologous cells for therapy. This “off-the-shelf” approach, much like the approach used in transfusion medicine, would allow for quicker availability of the cells to a greater number of patients, she said.
Dr. June who, along with Dr. Heslop, cochaired the SITC plenary session on genetically modified cell therapy, agreed, saying that if this approach works with T cells, it would radically change the CAR T landscape in terms of availability and, perhaps – eventually – cost.
Preliminary results from phase I studies (CALM and PALL) of this approach will be presented at the upcoming annual meeting of the American Society of Hematology. The studies are a joint effort by Servier and Cellectis, which joined forces in the development of UCART19, an allogeneic CAR-T product for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia.
Still, value remains an important consideration. If a therapy is expected to extend a pancreatic cancer patient’s life by a month, it’s probably valid to ask if that is cost effective, but if it is potentially curative for a patient with hematologic malignancy, it’s very hard to say they can’t access it, Dr. Heslop said.
Cost-saving proposals
Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.
Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.
In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.
“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.
In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.
In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.
“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.
The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.
Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).
“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.
The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.
Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.
“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”
Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.
Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.
“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.
In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
Price tag pressure
During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.
The “list price” for tisagenlecleucel is $475,000, and the potential patient pool is in the hundreds. The price for axicabtagene ciloleucel is $373,000, with a potential market in the thousands. Taking this into account, the global CAR T market is estimated at about $72 million and is projected to expand to nearly $3.5 billion in the next decade, said Dr. Maziarz, who is also chair of the Value and Health Economics Interest Group of the American Society for Blood and Marrow Transplantation.
The market for adoptive cell therapy overall – including transplant, CAR T, natural killer cells, and cell vaccines – is projected by some individuals to be worth $30 billion by 2030, he added, noting, for the sake of comparison, that the total estimated U.S. expenditure for all cancer care in the United States in 2010 was $125 billion.
At the heart of the issue of cost is the matter of value, he said.
“You can talk about price, and you can talk about cost, but … what we want to do with our dollars is buy value – and quality and value are very hard to measure,” he said, noting that he expects public and governmental backlash, as was seen with prior high-cost treatments such as Sovaldi for hepatitis C and Glybera for lipoprotein lipase deficiency.
Value-based payment is a recurrent theme in medicine, and these treatments came under intense scrutiny for their high costs. Sovaldi, for example, costs approximately $90,000 for a treatment course. That sounds like a lot of money, but it cures the disease and can prevent long-term complications, Dr. Maziarz said. Still, it received a lot of negative press, and the backlash was severe.
“People do respond to price,” he said, noting that he predicts the same for CAR T-cell therapies.
The costs of CAR T-cell therapy, particularly when taking into consideration the costs that hospitals will incur given the lymphodepletion that patients experience and the after-care required, will likely exceed those of most stem cell transplants and could easily reach the $1 million-plus estimates, Helen Heslop, MD, professor of medicine and pediatrics and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston, said in an interview.
Aside from the research and development costs, these treatments also cost more to make than any others previously made, according to Carl H. June, MD, the Richard W. Vague Professor In Immunotherapy at the University of Pennsylvania, Philadelphia, and a pioneer in CAR T-cell research.
Dr. June predicted that costs will be forced down over time because of process improvements and competition. “What’s unknown is the time span on how long it will take,” he said in an interview.
Groups like the United Kingdom’s National Institute for Health and Care Excellence (NICE) are already looking at value-based approaches to providing CAR T-cell therapy, Dr. Heslop said.
“I think there will need to be a lot more comparative effectiveness analyses done,” she said. “I know my institution started to look at the cost in a child with ALL once they relapse, and when you look at all the downstream cost, even though [CAR T-cell therapy] sounds very expensive, as a one-time therapy versus much longer treatment, it may actually be value based,” she said.
When it comes to improving access, one of the approaches being studied is the use of universal cell banks as opposed to autologous cells for therapy. This “off-the-shelf” approach, much like the approach used in transfusion medicine, would allow for quicker availability of the cells to a greater number of patients, she said.
Dr. June who, along with Dr. Heslop, cochaired the SITC plenary session on genetically modified cell therapy, agreed, saying that if this approach works with T cells, it would radically change the CAR T landscape in terms of availability and, perhaps – eventually – cost.
Preliminary results from phase I studies (CALM and PALL) of this approach will be presented at the upcoming annual meeting of the American Society of Hematology. The studies are a joint effort by Servier and Cellectis, which joined forces in the development of UCART19, an allogeneic CAR-T product for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia.
Still, value remains an important consideration. If a therapy is expected to extend a pancreatic cancer patient’s life by a month, it’s probably valid to ask if that is cost effective, but if it is potentially curative for a patient with hematologic malignancy, it’s very hard to say they can’t access it, Dr. Heslop said.
Cost-saving proposals
Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.
Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.
In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.
“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.
In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.
In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.
“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.
The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.
Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).
“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.
The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.
Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.
“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”
Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.
Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.
“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.
In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
Price tag pressure
During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.
The “list price” for tisagenlecleucel is $475,000, and the potential patient pool is in the hundreds. The price for axicabtagene ciloleucel is $373,000, with a potential market in the thousands. Taking this into account, the global CAR T market is estimated at about $72 million and is projected to expand to nearly $3.5 billion in the next decade, said Dr. Maziarz, who is also chair of the Value and Health Economics Interest Group of the American Society for Blood and Marrow Transplantation.
The market for adoptive cell therapy overall – including transplant, CAR T, natural killer cells, and cell vaccines – is projected by some individuals to be worth $30 billion by 2030, he added, noting, for the sake of comparison, that the total estimated U.S. expenditure for all cancer care in the United States in 2010 was $125 billion.
At the heart of the issue of cost is the matter of value, he said.
“You can talk about price, and you can talk about cost, but … what we want to do with our dollars is buy value – and quality and value are very hard to measure,” he said, noting that he expects public and governmental backlash, as was seen with prior high-cost treatments such as Sovaldi for hepatitis C and Glybera for lipoprotein lipase deficiency.
Value-based payment is a recurrent theme in medicine, and these treatments came under intense scrutiny for their high costs. Sovaldi, for example, costs approximately $90,000 for a treatment course. That sounds like a lot of money, but it cures the disease and can prevent long-term complications, Dr. Maziarz said. Still, it received a lot of negative press, and the backlash was severe.
“People do respond to price,” he said, noting that he predicts the same for CAR T-cell therapies.
The costs of CAR T-cell therapy, particularly when taking into consideration the costs that hospitals will incur given the lymphodepletion that patients experience and the after-care required, will likely exceed those of most stem cell transplants and could easily reach the $1 million-plus estimates, Helen Heslop, MD, professor of medicine and pediatrics and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston, said in an interview.
Aside from the research and development costs, these treatments also cost more to make than any others previously made, according to Carl H. June, MD, the Richard W. Vague Professor In Immunotherapy at the University of Pennsylvania, Philadelphia, and a pioneer in CAR T-cell research.
Dr. June predicted that costs will be forced down over time because of process improvements and competition. “What’s unknown is the time span on how long it will take,” he said in an interview.
Groups like the United Kingdom’s National Institute for Health and Care Excellence (NICE) are already looking at value-based approaches to providing CAR T-cell therapy, Dr. Heslop said.
“I think there will need to be a lot more comparative effectiveness analyses done,” she said. “I know my institution started to look at the cost in a child with ALL once they relapse, and when you look at all the downstream cost, even though [CAR T-cell therapy] sounds very expensive, as a one-time therapy versus much longer treatment, it may actually be value based,” she said.
When it comes to improving access, one of the approaches being studied is the use of universal cell banks as opposed to autologous cells for therapy. This “off-the-shelf” approach, much like the approach used in transfusion medicine, would allow for quicker availability of the cells to a greater number of patients, she said.
Dr. June who, along with Dr. Heslop, cochaired the SITC plenary session on genetically modified cell therapy, agreed, saying that if this approach works with T cells, it would radically change the CAR T landscape in terms of availability and, perhaps – eventually – cost.
Preliminary results from phase I studies (CALM and PALL) of this approach will be presented at the upcoming annual meeting of the American Society of Hematology. The studies are a joint effort by Servier and Cellectis, which joined forces in the development of UCART19, an allogeneic CAR-T product for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia.
Still, value remains an important consideration. If a therapy is expected to extend a pancreatic cancer patient’s life by a month, it’s probably valid to ask if that is cost effective, but if it is potentially curative for a patient with hematologic malignancy, it’s very hard to say they can’t access it, Dr. Heslop said.
Cost-saving proposals
Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.
Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.
In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.
“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.
In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.
In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.
“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.
The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.
Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).
“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.
The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.
Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.
“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”
Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.
Can increased scope of practice protect against family physician burnout?
MONTREAL – Have restrictions on scope of practice contributed to primary care physician burnout?
Perhaps they have, according to a recent survey that saw less burnout among recently graduated family physicians who retained inpatient or obstetrics work.
Of the 1,167 family practice physicians surveyed, 42% reported that they felt burned out once per week or more, said Amanda Weidner, MPH, of the University of Washington Family Medicine Residency Network in Seattle. However, some physicians were significantly less likely to experience burnout: those whose practice included adult inpatient medicine (P less than .0001), those currently delivering babies (P = .0007), and those who routinely saw their patients at the hospital or in patients’ homes (P = .0016 and P = .02, respectively).
Surveys of family practice physicians have reported varying levels of burnout, ranging from as low as 24% to as high as 65%. “Either way, we can probably agree that even one quarter of physicians saying they’re burned out is too many,” said Ms. Weidner during a presentation at the annual meeting of the National Association of Primary Care Research Groups.
Ms. Weidner and her colleagues polled young family practice physicians about their feelings of burnout and about their practice scope. She said she and her colleagues wondered about the association between those factors because the scope of primary care practice has been narrowing while primary care physicians have been reporting increasing levels of burnout – and at a higher rate than many other specialties.
Their survey, mailed in 2016, was sent to American Board of Family Medicine (ABFM) diplomates who were 2013 graduates of family practice residencies. Overall, 67% responded to the survey. Ms. Weidner and her colleagues used responses from the 78% of respondents who reported providing outpatient continuity care, rather than those who were hospitalists or who practiced in noncontinuity care areas, such as urgent care or emergency medicine.
Participants were asked to indicate how often they felt burned out in their work, with seven choices that ranged from “every day” to “never.” This single question from the Maslach Burnout Inventory, said Ms. Weidner, has been shown to correlate well with the emotional exhaustion domain of the inventory: Any response indicating feeling burned out at least once a week correlates with burnout.
In addition to asking physicians about the scope of their practice and their practice setting, the investigators assessed their work effort by asking about the number of patient encounters per day and whether respondents had after-hours calls and saw patients on weekends and evenings.
Respondents were, on average, about 36 years old, 58.6% were female, and 84.7% held an MD (rather than a DO). Two-thirds were graduates of U.S. medical schools.
Maintaining a broad scope of practice for family physicians can help fulfill the “triple aims” (enhancing patient experience, improving population health, and reducing costs) – now sometimes characterized as the “quadruple aims”with the addition of preventing burnout – of health system performance, said Ms. Weidner. In addition to proven cost reduction, she said, maintaining a broad scope of practice in family practice can enhance the patient experience and improve population health. If increased scope of practice also is associated with improved physician satisfaction, then it will also contribute to the fourth aim, she said.
Questioners in the audience asked Ms. Weidner and her collaborators to dive a little deeper into the data. One audience member remarked that she sees colleagues scheduling themselves for inpatient coverage or an afternoon of endometrial biopsies and other procedures as a strategy to avoid clinic time. She asked whether it’s the practice variety or the reduced number of clinic hours per week that’s driving the lower burnout rates.
Ms. Weidner acknowledged the possibility that working in other practice settings might reduce workload in terms of paperwork and patient communication. However, she pointed out that the number of hours worked per week was not associated with burnout; additionally, she said, both physicians who reported burnout and those who did not saw about the same number of patients per day.
Another audience member wondered whether some of the burnout – and practice restriction – is related to the fact that fewer physicians own their own practices. Maybe, he said, “There’s less of an obligation to be there to take people through all phases of life.”
Some practice restriction may be self-imposed, as may be the case when physicians don’t want the call obligations associated with obstetrics, but some of it is imposed by the system as an attempt to increase clinic throughput, Ms. Weidner said. “This is something for health systems to pay attention to. It’s less of an individual issue and more of a health system issue.”
Ms. Weidner reported that her work was supported by an ABFM Foundation grant while she was a visiting ABFM scholar.
koakes@frontlinemedcom.com
On Twitter @karioakes
MONTREAL – Have restrictions on scope of practice contributed to primary care physician burnout?
Perhaps they have, according to a recent survey that saw less burnout among recently graduated family physicians who retained inpatient or obstetrics work.
Of the 1,167 family practice physicians surveyed, 42% reported that they felt burned out once per week or more, said Amanda Weidner, MPH, of the University of Washington Family Medicine Residency Network in Seattle. However, some physicians were significantly less likely to experience burnout: those whose practice included adult inpatient medicine (P less than .0001), those currently delivering babies (P = .0007), and those who routinely saw their patients at the hospital or in patients’ homes (P = .0016 and P = .02, respectively).
Surveys of family practice physicians have reported varying levels of burnout, ranging from as low as 24% to as high as 65%. “Either way, we can probably agree that even one quarter of physicians saying they’re burned out is too many,” said Ms. Weidner during a presentation at the annual meeting of the National Association of Primary Care Research Groups.
Ms. Weidner and her colleagues polled young family practice physicians about their feelings of burnout and about their practice scope. She said she and her colleagues wondered about the association between those factors because the scope of primary care practice has been narrowing while primary care physicians have been reporting increasing levels of burnout – and at a higher rate than many other specialties.
Their survey, mailed in 2016, was sent to American Board of Family Medicine (ABFM) diplomates who were 2013 graduates of family practice residencies. Overall, 67% responded to the survey. Ms. Weidner and her colleagues used responses from the 78% of respondents who reported providing outpatient continuity care, rather than those who were hospitalists or who practiced in noncontinuity care areas, such as urgent care or emergency medicine.
Participants were asked to indicate how often they felt burned out in their work, with seven choices that ranged from “every day” to “never.” This single question from the Maslach Burnout Inventory, said Ms. Weidner, has been shown to correlate well with the emotional exhaustion domain of the inventory: Any response indicating feeling burned out at least once a week correlates with burnout.
In addition to asking physicians about the scope of their practice and their practice setting, the investigators assessed their work effort by asking about the number of patient encounters per day and whether respondents had after-hours calls and saw patients on weekends and evenings.
Respondents were, on average, about 36 years old, 58.6% were female, and 84.7% held an MD (rather than a DO). Two-thirds were graduates of U.S. medical schools.
Maintaining a broad scope of practice for family physicians can help fulfill the “triple aims” (enhancing patient experience, improving population health, and reducing costs) – now sometimes characterized as the “quadruple aims”with the addition of preventing burnout – of health system performance, said Ms. Weidner. In addition to proven cost reduction, she said, maintaining a broad scope of practice in family practice can enhance the patient experience and improve population health. If increased scope of practice also is associated with improved physician satisfaction, then it will also contribute to the fourth aim, she said.
Questioners in the audience asked Ms. Weidner and her collaborators to dive a little deeper into the data. One audience member remarked that she sees colleagues scheduling themselves for inpatient coverage or an afternoon of endometrial biopsies and other procedures as a strategy to avoid clinic time. She asked whether it’s the practice variety or the reduced number of clinic hours per week that’s driving the lower burnout rates.
Ms. Weidner acknowledged the possibility that working in other practice settings might reduce workload in terms of paperwork and patient communication. However, she pointed out that the number of hours worked per week was not associated with burnout; additionally, she said, both physicians who reported burnout and those who did not saw about the same number of patients per day.
Another audience member wondered whether some of the burnout – and practice restriction – is related to the fact that fewer physicians own their own practices. Maybe, he said, “There’s less of an obligation to be there to take people through all phases of life.”
Some practice restriction may be self-imposed, as may be the case when physicians don’t want the call obligations associated with obstetrics, but some of it is imposed by the system as an attempt to increase clinic throughput, Ms. Weidner said. “This is something for health systems to pay attention to. It’s less of an individual issue and more of a health system issue.”
Ms. Weidner reported that her work was supported by an ABFM Foundation grant while she was a visiting ABFM scholar.
koakes@frontlinemedcom.com
On Twitter @karioakes
MONTREAL – Have restrictions on scope of practice contributed to primary care physician burnout?
Perhaps they have, according to a recent survey that saw less burnout among recently graduated family physicians who retained inpatient or obstetrics work.
Of the 1,167 family practice physicians surveyed, 42% reported that they felt burned out once per week or more, said Amanda Weidner, MPH, of the University of Washington Family Medicine Residency Network in Seattle. However, some physicians were significantly less likely to experience burnout: those whose practice included adult inpatient medicine (P less than .0001), those currently delivering babies (P = .0007), and those who routinely saw their patients at the hospital or in patients’ homes (P = .0016 and P = .02, respectively).
Surveys of family practice physicians have reported varying levels of burnout, ranging from as low as 24% to as high as 65%. “Either way, we can probably agree that even one quarter of physicians saying they’re burned out is too many,” said Ms. Weidner during a presentation at the annual meeting of the National Association of Primary Care Research Groups.
Ms. Weidner and her colleagues polled young family practice physicians about their feelings of burnout and about their practice scope. She said she and her colleagues wondered about the association between those factors because the scope of primary care practice has been narrowing while primary care physicians have been reporting increasing levels of burnout – and at a higher rate than many other specialties.
Their survey, mailed in 2016, was sent to American Board of Family Medicine (ABFM) diplomates who were 2013 graduates of family practice residencies. Overall, 67% responded to the survey. Ms. Weidner and her colleagues used responses from the 78% of respondents who reported providing outpatient continuity care, rather than those who were hospitalists or who practiced in noncontinuity care areas, such as urgent care or emergency medicine.
Participants were asked to indicate how often they felt burned out in their work, with seven choices that ranged from “every day” to “never.” This single question from the Maslach Burnout Inventory, said Ms. Weidner, has been shown to correlate well with the emotional exhaustion domain of the inventory: Any response indicating feeling burned out at least once a week correlates with burnout.
In addition to asking physicians about the scope of their practice and their practice setting, the investigators assessed their work effort by asking about the number of patient encounters per day and whether respondents had after-hours calls and saw patients on weekends and evenings.
Respondents were, on average, about 36 years old, 58.6% were female, and 84.7% held an MD (rather than a DO). Two-thirds were graduates of U.S. medical schools.
Maintaining a broad scope of practice for family physicians can help fulfill the “triple aims” (enhancing patient experience, improving population health, and reducing costs) – now sometimes characterized as the “quadruple aims”with the addition of preventing burnout – of health system performance, said Ms. Weidner. In addition to proven cost reduction, she said, maintaining a broad scope of practice in family practice can enhance the patient experience and improve population health. If increased scope of practice also is associated with improved physician satisfaction, then it will also contribute to the fourth aim, she said.
Questioners in the audience asked Ms. Weidner and her collaborators to dive a little deeper into the data. One audience member remarked that she sees colleagues scheduling themselves for inpatient coverage or an afternoon of endometrial biopsies and other procedures as a strategy to avoid clinic time. She asked whether it’s the practice variety or the reduced number of clinic hours per week that’s driving the lower burnout rates.
Ms. Weidner acknowledged the possibility that working in other practice settings might reduce workload in terms of paperwork and patient communication. However, she pointed out that the number of hours worked per week was not associated with burnout; additionally, she said, both physicians who reported burnout and those who did not saw about the same number of patients per day.
Another audience member wondered whether some of the burnout – and practice restriction – is related to the fact that fewer physicians own their own practices. Maybe, he said, “There’s less of an obligation to be there to take people through all phases of life.”
Some practice restriction may be self-imposed, as may be the case when physicians don’t want the call obligations associated with obstetrics, but some of it is imposed by the system as an attempt to increase clinic throughput, Ms. Weidner said. “This is something for health systems to pay attention to. It’s less of an individual issue and more of a health system issue.”
Ms. Weidner reported that her work was supported by an ABFM Foundation grant while she was a visiting ABFM scholar.
koakes@frontlinemedcom.com
On Twitter @karioakes
AT NAPCRG 2017
Key clinical point:
Major finding: Doing inpatient work and delivering babies was associated with less burnout for recent graduates (P less than .0001 and P = .007).
Data source: A 2016 survey of American Board of Family Medicine (ABFM) diplomates who were 2013 graduates of residency programs; 1,167 physicians’ practices met inclusion criteria.
Disclosures: Ms. Weidner reported that her work was supported by an ABFM Foundation grant while she was a visiting ABFM scholar.
ADHD and the role of wellness
ADHD is a very common disorder with several medication treatment options. There also are wellness and parenting strategies that can address aspects of the challenges of ADHD that are not perfectly covered by medication, such as excess symptoms, times of day that are not covered, or oppositional behavior that often develops secondarily.
Case summary
James is a 6-year-old boy who has been an active, high-energy child since preschool. He has had difficulty with wiggling around in kindergarten and preschool, talking excessively, and being unable to follow directions and pay attention. He is impulsive, disruptive, and frequently doesn’t listen to what his parents tell him to do. Parents and teachers rank him in the clinical range for hyperactivity, impulsivity, and attention problems on standardized rating scales.
Discussion
When we first discuss a new diagnosis with a family, we have the opportunity to shape the family’s expectations about that diagnosis and how it should be addressed. When I discuss ADHD with a new family, I want them to understand the symptoms of inattention, hyperactivity, and impulsiveness, and that these symptoms are not the child’s fault, but rather related to the way his brain is connected. At the same time, I also emphasize that these connections are not entirely fixed, that they mature over time, and that they are affected by experiences in life. In particular, I stress that positive experiences and wellness activities can influence the brain in a positive way. While, of course, I discuss the range of medications that can address these issues, I also deal with wellness in the treatment plan.
Exercise
Studies in humans and animals have provided background evidence that exercise increases the release of neurotransmitters such as dopamine and norepinephrine that are important in the pathophysiology of ADHD. Cerillo-Urbina et al. did a meta-analysis in 2015 of randomized controlled trials and found medium to large effect sizes for a variety of physical activity programs with respect to attention, hyperactivity, and impulsivity, although the study quality was generally low.1 Clearly we need additional more rigorous studies, but given the positive direction of outcomes, the lack of side effects, and the many other positive effects of exercise, it does not seem too soon to add exercise as a prescription for our patients with ADHD. I review this evidence with families, ask them about physical activity they like, and ask if they are willing to work toward an hour of exercise a day.
Sleep
Many children with ADHD have problems with sleep even before they start on stimulant medications, which can further affect sleep. Addressing sleep early on can improve ADHD symptoms, as well as help parents change or avoid patterns like having children fall asleep to the sound of a television. Brief sleep hygiene and cognitive-behavioral therapy interventions over three visits were demonstrated in a randomized controlled trial by Hisock et al. to improve ADHD symptoms and behavioral function.2 These psychosocial interventions clearly are the first line in addressing sleep problems in ADHD, and can benefit even sleep problems connected to medication.
Parent training
Treatment plan
1. Have the child exercise 1 hour every day. Have fun!
2. Establish a nightly bedtime routine, with a bath at 7:30 p.m., brushing of teeth, a story, and lights out at 8 with no TV in the room.
3. Check out the CHADD website for Parent to Parent.
4. Start a trial of stimulant medication.
5. Return in 2 weeks to monitor these interventions, adjust goals, and adjust medications.
When to refer
Many parents will be able to put such a plan in motion with your support and that of other parents. If they are struggling, therapists, psychologists, and psychiatrists trained in motivational and behavioral methods can provide more individualized parent training. Also consider whether the parents themselves may have ADHD and could use referral and treatment.
Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.
References
1. Child Care Health Dev. 2015 Nov;41(6):779-88.
2. BMJ. 2015. doi: 10.1136/bmj.h68.
ADHD is a very common disorder with several medication treatment options. There also are wellness and parenting strategies that can address aspects of the challenges of ADHD that are not perfectly covered by medication, such as excess symptoms, times of day that are not covered, or oppositional behavior that often develops secondarily.
Case summary
James is a 6-year-old boy who has been an active, high-energy child since preschool. He has had difficulty with wiggling around in kindergarten and preschool, talking excessively, and being unable to follow directions and pay attention. He is impulsive, disruptive, and frequently doesn’t listen to what his parents tell him to do. Parents and teachers rank him in the clinical range for hyperactivity, impulsivity, and attention problems on standardized rating scales.
Discussion
When we first discuss a new diagnosis with a family, we have the opportunity to shape the family’s expectations about that diagnosis and how it should be addressed. When I discuss ADHD with a new family, I want them to understand the symptoms of inattention, hyperactivity, and impulsiveness, and that these symptoms are not the child’s fault, but rather related to the way his brain is connected. At the same time, I also emphasize that these connections are not entirely fixed, that they mature over time, and that they are affected by experiences in life. In particular, I stress that positive experiences and wellness activities can influence the brain in a positive way. While, of course, I discuss the range of medications that can address these issues, I also deal with wellness in the treatment plan.
Exercise
Studies in humans and animals have provided background evidence that exercise increases the release of neurotransmitters such as dopamine and norepinephrine that are important in the pathophysiology of ADHD. Cerillo-Urbina et al. did a meta-analysis in 2015 of randomized controlled trials and found medium to large effect sizes for a variety of physical activity programs with respect to attention, hyperactivity, and impulsivity, although the study quality was generally low.1 Clearly we need additional more rigorous studies, but given the positive direction of outcomes, the lack of side effects, and the many other positive effects of exercise, it does not seem too soon to add exercise as a prescription for our patients with ADHD. I review this evidence with families, ask them about physical activity they like, and ask if they are willing to work toward an hour of exercise a day.
Sleep
Many children with ADHD have problems with sleep even before they start on stimulant medications, which can further affect sleep. Addressing sleep early on can improve ADHD symptoms, as well as help parents change or avoid patterns like having children fall asleep to the sound of a television. Brief sleep hygiene and cognitive-behavioral therapy interventions over three visits were demonstrated in a randomized controlled trial by Hisock et al. to improve ADHD symptoms and behavioral function.2 These psychosocial interventions clearly are the first line in addressing sleep problems in ADHD, and can benefit even sleep problems connected to medication.
Parent training
Treatment plan
1. Have the child exercise 1 hour every day. Have fun!
2. Establish a nightly bedtime routine, with a bath at 7:30 p.m., brushing of teeth, a story, and lights out at 8 with no TV in the room.
3. Check out the CHADD website for Parent to Parent.
4. Start a trial of stimulant medication.
5. Return in 2 weeks to monitor these interventions, adjust goals, and adjust medications.
When to refer
Many parents will be able to put such a plan in motion with your support and that of other parents. If they are struggling, therapists, psychologists, and psychiatrists trained in motivational and behavioral methods can provide more individualized parent training. Also consider whether the parents themselves may have ADHD and could use referral and treatment.
Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.
References
1. Child Care Health Dev. 2015 Nov;41(6):779-88.
2. BMJ. 2015. doi: 10.1136/bmj.h68.
ADHD is a very common disorder with several medication treatment options. There also are wellness and parenting strategies that can address aspects of the challenges of ADHD that are not perfectly covered by medication, such as excess symptoms, times of day that are not covered, or oppositional behavior that often develops secondarily.
Case summary
James is a 6-year-old boy who has been an active, high-energy child since preschool. He has had difficulty with wiggling around in kindergarten and preschool, talking excessively, and being unable to follow directions and pay attention. He is impulsive, disruptive, and frequently doesn’t listen to what his parents tell him to do. Parents and teachers rank him in the clinical range for hyperactivity, impulsivity, and attention problems on standardized rating scales.
Discussion
When we first discuss a new diagnosis with a family, we have the opportunity to shape the family’s expectations about that diagnosis and how it should be addressed. When I discuss ADHD with a new family, I want them to understand the symptoms of inattention, hyperactivity, and impulsiveness, and that these symptoms are not the child’s fault, but rather related to the way his brain is connected. At the same time, I also emphasize that these connections are not entirely fixed, that they mature over time, and that they are affected by experiences in life. In particular, I stress that positive experiences and wellness activities can influence the brain in a positive way. While, of course, I discuss the range of medications that can address these issues, I also deal with wellness in the treatment plan.
Exercise
Studies in humans and animals have provided background evidence that exercise increases the release of neurotransmitters such as dopamine and norepinephrine that are important in the pathophysiology of ADHD. Cerillo-Urbina et al. did a meta-analysis in 2015 of randomized controlled trials and found medium to large effect sizes for a variety of physical activity programs with respect to attention, hyperactivity, and impulsivity, although the study quality was generally low.1 Clearly we need additional more rigorous studies, but given the positive direction of outcomes, the lack of side effects, and the many other positive effects of exercise, it does not seem too soon to add exercise as a prescription for our patients with ADHD. I review this evidence with families, ask them about physical activity they like, and ask if they are willing to work toward an hour of exercise a day.
Sleep
Many children with ADHD have problems with sleep even before they start on stimulant medications, which can further affect sleep. Addressing sleep early on can improve ADHD symptoms, as well as help parents change or avoid patterns like having children fall asleep to the sound of a television. Brief sleep hygiene and cognitive-behavioral therapy interventions over three visits were demonstrated in a randomized controlled trial by Hisock et al. to improve ADHD symptoms and behavioral function.2 These psychosocial interventions clearly are the first line in addressing sleep problems in ADHD, and can benefit even sleep problems connected to medication.
Parent training
Treatment plan
1. Have the child exercise 1 hour every day. Have fun!
2. Establish a nightly bedtime routine, with a bath at 7:30 p.m., brushing of teeth, a story, and lights out at 8 with no TV in the room.
3. Check out the CHADD website for Parent to Parent.
4. Start a trial of stimulant medication.
5. Return in 2 weeks to monitor these interventions, adjust goals, and adjust medications.
When to refer
Many parents will be able to put such a plan in motion with your support and that of other parents. If they are struggling, therapists, psychologists, and psychiatrists trained in motivational and behavioral methods can provide more individualized parent training. Also consider whether the parents themselves may have ADHD and could use referral and treatment.
Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.
References
1. Child Care Health Dev. 2015 Nov;41(6):779-88.
2. BMJ. 2015. doi: 10.1136/bmj.h68.
Emerging sickle cell agents target new pathways
CONCORD, N.C. – Approved treatments for sickle cell disease have been extremely limited, but there are several therapies in the research pipeline that use new pathways to target the disease.
“We do have much better understanding of the pathophysiology, which is getting us a few more targets to aim at,” Julie Kanter, MD, director of sickle cell research at the Medical University of South Carolina, Charleston, said at Sickle Cell Disease Symposium held by Carolinas Health Care System. These targets include influencing how cells interact with the vascular endothelium, inhibiting platelets, and preventing cell sickling and inflammation.
“I’m waiting to see who’s willing to take it just because it is a lot of powder that the patient has to mix and drink twice a day, but it does look promising to reduce inflammation,” Dr. Kanter said.
SCD pipeline
Deeper in the sickle cell pipeline is a class of antisickling agents known as hemoglobin modifiers. “We’re tying to change the way hemoglobin binds to oxygen, and if we can keep hemoglobin binding to oxygen longer, it actually decreases the risk of hemoglobin sickling and polymerizing in the cell,” Dr. Kanter explained.
One hemoglobin modifier is voxelotor (previously called GBT440), a once-daily oral agent that Global Blood Therapeutics has in development.
Another category of antisickling agents that researchers are looking at is anti-inflammatory moderators, Dr. Kanter said. These include nitric oxide donors like sildenafil, which did not “quite work” in SCD, and arginine and glutamine, which increase the amount of nitric oxide once in the body “and hopefully reduce the risk of sickling,” she said. “If we can improve inflammation, we might be able to improve the risk of crisis.”
Cell adhesion modifiers are a drug class that aims to prevent cells from binding to each other. These include platelet inhibitors and endothelial blockers. “There are several antiplatelet agents that are approved really for stroke prevention or heart attack prevention, and we’re trying to see if we can repurpose these in sickle cell disease in a specific pathway that allows the platelet to stick to the endothelium, but if we only inhibit one pathway it should not increase the risk of bleeding,” Dr. Kanter said.
One platelet inhibition pathway that researchers are focused on is the P2Y12 adenosine diphosphate blockade, which the platelet inhibitor prasugrel (Effient) acts on. A 2016 study of this pathway in SCD “wasn’t successful,” Dr. Kanter said, “but it had some interesting results” – namely that the drug may be most effective in adolescents (N Engl J Med. 2016 Feb 18;374[7]:625-35).
Selectin-blocking medications are a drug class that act on white blood cell adhesion to, and movement through, the endothelium, Dr. Kanter said. “Neutrophils can instigate a sickle cell crisis, so if we can interrupt some of this rolling or sticking, could we decrease the risk of a sickle cell crisis?” The drug GMI-1070 is currently being studied in a phase III trial and so far has shown “a significant decrease in the amount of opioids used by those individuals who received the study drug,” she said.
Crizanlizumab (also known as SelG1) is a humanized monoclonal antibody with an affinity to P-selectin and is the subject of the phase II SUSTAIN trial, which included a cohort that also was taking hydroxyurea. Treatment with high-dose crizanlizumab resulted in an annual rate of sickle cell–related pain crises that was more than 45% lower than with placebo (N Engl J Med. 2017 Feb 2;376[5]:429-39).
Stem cell transplants
Besides drugs, stem cell transplants to treat SCD have advanced in recent years to the point where cure rates are exceeding 90%, Dr. Kanter noted. “However, the real issue with stem cells is that patients still don’t have enough donors,” she said.
SCD is also potentially amenable to gene therapy, Dr. Kanter said, noting that SCD gene therapy trials in progress are looking at harvesting patients’ own bone marrow, using the lentivirus viral vector, inserting a gene to increase production of nonsickle hemoglobin, and using myeloablative chemotherapy to remove old marrow and replace it with new, manipulated bone marrow.
Several programs are investigating using a gene editing technique, known as CRISPR/Cas9, to alter the BCL11A gene to maintain fetal hemoglobin production.
“We all make fetal hemoglobin at birth, and then over 6 months to 1 year of life, our bodies convert fetal hemoglobin to adult hemoglobin,” she said. “In sickle cell disease, it converts to sickle hemoglobin. What if we could prevent that conversion and keep the fetal hemoglobin turned on?” That could potentially eradicate the complications of SCD starting at an early age, Dr. Kanter said.
Dr. Kanter, who has been involved in several of the SCD trials, reported relationships with Pfizer, AstraZeneca, Bluebird Bio, Global Blood Therapeutics, Novartis, Guidepoint, GLG, ApoPharma, and Purdue Pharma.
CONCORD, N.C. – Approved treatments for sickle cell disease have been extremely limited, but there are several therapies in the research pipeline that use new pathways to target the disease.
“We do have much better understanding of the pathophysiology, which is getting us a few more targets to aim at,” Julie Kanter, MD, director of sickle cell research at the Medical University of South Carolina, Charleston, said at Sickle Cell Disease Symposium held by Carolinas Health Care System. These targets include influencing how cells interact with the vascular endothelium, inhibiting platelets, and preventing cell sickling and inflammation.
“I’m waiting to see who’s willing to take it just because it is a lot of powder that the patient has to mix and drink twice a day, but it does look promising to reduce inflammation,” Dr. Kanter said.
SCD pipeline
Deeper in the sickle cell pipeline is a class of antisickling agents known as hemoglobin modifiers. “We’re tying to change the way hemoglobin binds to oxygen, and if we can keep hemoglobin binding to oxygen longer, it actually decreases the risk of hemoglobin sickling and polymerizing in the cell,” Dr. Kanter explained.
One hemoglobin modifier is voxelotor (previously called GBT440), a once-daily oral agent that Global Blood Therapeutics has in development.
Another category of antisickling agents that researchers are looking at is anti-inflammatory moderators, Dr. Kanter said. These include nitric oxide donors like sildenafil, which did not “quite work” in SCD, and arginine and glutamine, which increase the amount of nitric oxide once in the body “and hopefully reduce the risk of sickling,” she said. “If we can improve inflammation, we might be able to improve the risk of crisis.”
Cell adhesion modifiers are a drug class that aims to prevent cells from binding to each other. These include platelet inhibitors and endothelial blockers. “There are several antiplatelet agents that are approved really for stroke prevention or heart attack prevention, and we’re trying to see if we can repurpose these in sickle cell disease in a specific pathway that allows the platelet to stick to the endothelium, but if we only inhibit one pathway it should not increase the risk of bleeding,” Dr. Kanter said.
One platelet inhibition pathway that researchers are focused on is the P2Y12 adenosine diphosphate blockade, which the platelet inhibitor prasugrel (Effient) acts on. A 2016 study of this pathway in SCD “wasn’t successful,” Dr. Kanter said, “but it had some interesting results” – namely that the drug may be most effective in adolescents (N Engl J Med. 2016 Feb 18;374[7]:625-35).
Selectin-blocking medications are a drug class that act on white blood cell adhesion to, and movement through, the endothelium, Dr. Kanter said. “Neutrophils can instigate a sickle cell crisis, so if we can interrupt some of this rolling or sticking, could we decrease the risk of a sickle cell crisis?” The drug GMI-1070 is currently being studied in a phase III trial and so far has shown “a significant decrease in the amount of opioids used by those individuals who received the study drug,” she said.
Crizanlizumab (also known as SelG1) is a humanized monoclonal antibody with an affinity to P-selectin and is the subject of the phase II SUSTAIN trial, which included a cohort that also was taking hydroxyurea. Treatment with high-dose crizanlizumab resulted in an annual rate of sickle cell–related pain crises that was more than 45% lower than with placebo (N Engl J Med. 2017 Feb 2;376[5]:429-39).
Stem cell transplants
Besides drugs, stem cell transplants to treat SCD have advanced in recent years to the point where cure rates are exceeding 90%, Dr. Kanter noted. “However, the real issue with stem cells is that patients still don’t have enough donors,” she said.
SCD is also potentially amenable to gene therapy, Dr. Kanter said, noting that SCD gene therapy trials in progress are looking at harvesting patients’ own bone marrow, using the lentivirus viral vector, inserting a gene to increase production of nonsickle hemoglobin, and using myeloablative chemotherapy to remove old marrow and replace it with new, manipulated bone marrow.
Several programs are investigating using a gene editing technique, known as CRISPR/Cas9, to alter the BCL11A gene to maintain fetal hemoglobin production.
“We all make fetal hemoglobin at birth, and then over 6 months to 1 year of life, our bodies convert fetal hemoglobin to adult hemoglobin,” she said. “In sickle cell disease, it converts to sickle hemoglobin. What if we could prevent that conversion and keep the fetal hemoglobin turned on?” That could potentially eradicate the complications of SCD starting at an early age, Dr. Kanter said.
Dr. Kanter, who has been involved in several of the SCD trials, reported relationships with Pfizer, AstraZeneca, Bluebird Bio, Global Blood Therapeutics, Novartis, Guidepoint, GLG, ApoPharma, and Purdue Pharma.
CONCORD, N.C. – Approved treatments for sickle cell disease have been extremely limited, but there are several therapies in the research pipeline that use new pathways to target the disease.
“We do have much better understanding of the pathophysiology, which is getting us a few more targets to aim at,” Julie Kanter, MD, director of sickle cell research at the Medical University of South Carolina, Charleston, said at Sickle Cell Disease Symposium held by Carolinas Health Care System. These targets include influencing how cells interact with the vascular endothelium, inhibiting platelets, and preventing cell sickling and inflammation.
“I’m waiting to see who’s willing to take it just because it is a lot of powder that the patient has to mix and drink twice a day, but it does look promising to reduce inflammation,” Dr. Kanter said.
SCD pipeline
Deeper in the sickle cell pipeline is a class of antisickling agents known as hemoglobin modifiers. “We’re tying to change the way hemoglobin binds to oxygen, and if we can keep hemoglobin binding to oxygen longer, it actually decreases the risk of hemoglobin sickling and polymerizing in the cell,” Dr. Kanter explained.
One hemoglobin modifier is voxelotor (previously called GBT440), a once-daily oral agent that Global Blood Therapeutics has in development.
Another category of antisickling agents that researchers are looking at is anti-inflammatory moderators, Dr. Kanter said. These include nitric oxide donors like sildenafil, which did not “quite work” in SCD, and arginine and glutamine, which increase the amount of nitric oxide once in the body “and hopefully reduce the risk of sickling,” she said. “If we can improve inflammation, we might be able to improve the risk of crisis.”
Cell adhesion modifiers are a drug class that aims to prevent cells from binding to each other. These include platelet inhibitors and endothelial blockers. “There are several antiplatelet agents that are approved really for stroke prevention or heart attack prevention, and we’re trying to see if we can repurpose these in sickle cell disease in a specific pathway that allows the platelet to stick to the endothelium, but if we only inhibit one pathway it should not increase the risk of bleeding,” Dr. Kanter said.
One platelet inhibition pathway that researchers are focused on is the P2Y12 adenosine diphosphate blockade, which the platelet inhibitor prasugrel (Effient) acts on. A 2016 study of this pathway in SCD “wasn’t successful,” Dr. Kanter said, “but it had some interesting results” – namely that the drug may be most effective in adolescents (N Engl J Med. 2016 Feb 18;374[7]:625-35).
Selectin-blocking medications are a drug class that act on white blood cell adhesion to, and movement through, the endothelium, Dr. Kanter said. “Neutrophils can instigate a sickle cell crisis, so if we can interrupt some of this rolling or sticking, could we decrease the risk of a sickle cell crisis?” The drug GMI-1070 is currently being studied in a phase III trial and so far has shown “a significant decrease in the amount of opioids used by those individuals who received the study drug,” she said.
Crizanlizumab (also known as SelG1) is a humanized monoclonal antibody with an affinity to P-selectin and is the subject of the phase II SUSTAIN trial, which included a cohort that also was taking hydroxyurea. Treatment with high-dose crizanlizumab resulted in an annual rate of sickle cell–related pain crises that was more than 45% lower than with placebo (N Engl J Med. 2017 Feb 2;376[5]:429-39).
Stem cell transplants
Besides drugs, stem cell transplants to treat SCD have advanced in recent years to the point where cure rates are exceeding 90%, Dr. Kanter noted. “However, the real issue with stem cells is that patients still don’t have enough donors,” she said.
SCD is also potentially amenable to gene therapy, Dr. Kanter said, noting that SCD gene therapy trials in progress are looking at harvesting patients’ own bone marrow, using the lentivirus viral vector, inserting a gene to increase production of nonsickle hemoglobin, and using myeloablative chemotherapy to remove old marrow and replace it with new, manipulated bone marrow.
Several programs are investigating using a gene editing technique, known as CRISPR/Cas9, to alter the BCL11A gene to maintain fetal hemoglobin production.
“We all make fetal hemoglobin at birth, and then over 6 months to 1 year of life, our bodies convert fetal hemoglobin to adult hemoglobin,” she said. “In sickle cell disease, it converts to sickle hemoglobin. What if we could prevent that conversion and keep the fetal hemoglobin turned on?” That could potentially eradicate the complications of SCD starting at an early age, Dr. Kanter said.
Dr. Kanter, who has been involved in several of the SCD trials, reported relationships with Pfizer, AstraZeneca, Bluebird Bio, Global Blood Therapeutics, Novartis, Guidepoint, GLG, ApoPharma, and Purdue Pharma.
EXPERT ANALYSIS FROM A MEETING ON SICKLE CELL DISEASE
ACC survey: Burnout pervasive in cardiologists
ANAHEIM, CALIF. – A disturbingly high 27% of U.S. cardiologists reported currently feeling burnout in the American College of Cardiology’s third Professional Life Survey, Laxmi S. Mehta, MD, said at the American Heart Association scientific sessions.
A gender gap existed: The prevalence of burnout was 29% greater among female cardiologists than their male counterparts, by a margin of 31%-24%.
“These are the doctors who are taking care of people’s hearts, and we know that when you’re burned out, there are higher rates of medical errors and the quality of care is poorer. So this is problematic,” she said in an interview.
Burnout had a negative effect on career satisfaction: While 94% of cardiologists in the nonburnout group professed they were satisfied with their career, that was the case for only 74% of cardiologists who felt burnout. Just 56% percent of the burnout group said they would recommend cardiology as a career, compared with 80% of the practitioners who felt no burnout.
The 2015 ACC survey was completed by 2,313 U.S. cardiologists, 964 of whom were women. The first round of results, which focused on career satisfaction and racial and gender discrimination in the workplace, have been published (J Am Coll Cardiol. 2017 Jan 31;69[4]:452-62). The survey included the validated 10-question Mini Z burnout assessment, the results of which were the focus of the new analysis.
The 27% of cardiologists in the burnout group fell into three subcategories, the largest of which comprised those who reported feeling at least one burnout symptom of physical or mental exhaustion. Those who said their burnout symptoms don’t go away and that they think about their work frustrations frequently made up a smaller group. Just a few percent of survey participants fell into the completely burned out category.
Only 51% of the burnout group were satisfied with their financial compensation, compared with 68% of the nonburnout group. Sixty-one percent of the burnout group felt they were treated fairly at their job, as did 86% of the cardiologists who felt burnout. Half of the cardiologists with burnout reported experiencing past discrimination, compared with 37% of the nonburnout group. And 40% of the burnout group felt their family responsibilities hindered career advancement, a sentiment expressed by 22% of the nonburnout group.
EMR “pajama time” cited as a major burden
Two-thirds of cardiologists with constant burnout symptoms or complete burnout cited excessive time spent completing their electronic medical records as a significant contributing factor.
“The electronic medical record ends up taking over our personal time,” according to Dr. Mehta. “We call it ‘pajama time’ because many of us are doing the charts or responding to patients at midnight, on vacation, at meetings like this. There is no separation, and that’s a problem.”
What can be done to reduce burnout
The 2015 Professional Life Survey was the third one in 20 years. Compared with the earlier two, the most recent survey painted a picture of an aging workforce that is less likely to be in private practice. The survey – the first one to assess burnout within the specialty – was carried out by the ACC Women in Cardiology Leadership Council. Armed with the survey results, the ACC leadership is now in the process of redefining the organization’s mission statement to incorporate a new emphasis on providing for physician health and well-being in addition to the more traditional goals of improving the quality and reducing the cost of care.
“Many cardiologists are working a lot harder than they used to, with less personal time. We need to work on mechanisms to reduce burnout by reducing the burdens put on them. The survey data help because they show the cardiology profession, and hopefully hospital administrators, the importance of making a better work environment. That’s the hope,” Dr. Mehta said.
She reported having no financial conflicts of interest regarding the survey.
ANAHEIM, CALIF. – A disturbingly high 27% of U.S. cardiologists reported currently feeling burnout in the American College of Cardiology’s third Professional Life Survey, Laxmi S. Mehta, MD, said at the American Heart Association scientific sessions.
A gender gap existed: The prevalence of burnout was 29% greater among female cardiologists than their male counterparts, by a margin of 31%-24%.
“These are the doctors who are taking care of people’s hearts, and we know that when you’re burned out, there are higher rates of medical errors and the quality of care is poorer. So this is problematic,” she said in an interview.
Burnout had a negative effect on career satisfaction: While 94% of cardiologists in the nonburnout group professed they were satisfied with their career, that was the case for only 74% of cardiologists who felt burnout. Just 56% percent of the burnout group said they would recommend cardiology as a career, compared with 80% of the practitioners who felt no burnout.
The 2015 ACC survey was completed by 2,313 U.S. cardiologists, 964 of whom were women. The first round of results, which focused on career satisfaction and racial and gender discrimination in the workplace, have been published (J Am Coll Cardiol. 2017 Jan 31;69[4]:452-62). The survey included the validated 10-question Mini Z burnout assessment, the results of which were the focus of the new analysis.
The 27% of cardiologists in the burnout group fell into three subcategories, the largest of which comprised those who reported feeling at least one burnout symptom of physical or mental exhaustion. Those who said their burnout symptoms don’t go away and that they think about their work frustrations frequently made up a smaller group. Just a few percent of survey participants fell into the completely burned out category.
Only 51% of the burnout group were satisfied with their financial compensation, compared with 68% of the nonburnout group. Sixty-one percent of the burnout group felt they were treated fairly at their job, as did 86% of the cardiologists who felt burnout. Half of the cardiologists with burnout reported experiencing past discrimination, compared with 37% of the nonburnout group. And 40% of the burnout group felt their family responsibilities hindered career advancement, a sentiment expressed by 22% of the nonburnout group.
EMR “pajama time” cited as a major burden
Two-thirds of cardiologists with constant burnout symptoms or complete burnout cited excessive time spent completing their electronic medical records as a significant contributing factor.
“The electronic medical record ends up taking over our personal time,” according to Dr. Mehta. “We call it ‘pajama time’ because many of us are doing the charts or responding to patients at midnight, on vacation, at meetings like this. There is no separation, and that’s a problem.”
What can be done to reduce burnout
The 2015 Professional Life Survey was the third one in 20 years. Compared with the earlier two, the most recent survey painted a picture of an aging workforce that is less likely to be in private practice. The survey – the first one to assess burnout within the specialty – was carried out by the ACC Women in Cardiology Leadership Council. Armed with the survey results, the ACC leadership is now in the process of redefining the organization’s mission statement to incorporate a new emphasis on providing for physician health and well-being in addition to the more traditional goals of improving the quality and reducing the cost of care.
“Many cardiologists are working a lot harder than they used to, with less personal time. We need to work on mechanisms to reduce burnout by reducing the burdens put on them. The survey data help because they show the cardiology profession, and hopefully hospital administrators, the importance of making a better work environment. That’s the hope,” Dr. Mehta said.
She reported having no financial conflicts of interest regarding the survey.
ANAHEIM, CALIF. – A disturbingly high 27% of U.S. cardiologists reported currently feeling burnout in the American College of Cardiology’s third Professional Life Survey, Laxmi S. Mehta, MD, said at the American Heart Association scientific sessions.
A gender gap existed: The prevalence of burnout was 29% greater among female cardiologists than their male counterparts, by a margin of 31%-24%.
“These are the doctors who are taking care of people’s hearts, and we know that when you’re burned out, there are higher rates of medical errors and the quality of care is poorer. So this is problematic,” she said in an interview.
Burnout had a negative effect on career satisfaction: While 94% of cardiologists in the nonburnout group professed they were satisfied with their career, that was the case for only 74% of cardiologists who felt burnout. Just 56% percent of the burnout group said they would recommend cardiology as a career, compared with 80% of the practitioners who felt no burnout.
The 2015 ACC survey was completed by 2,313 U.S. cardiologists, 964 of whom were women. The first round of results, which focused on career satisfaction and racial and gender discrimination in the workplace, have been published (J Am Coll Cardiol. 2017 Jan 31;69[4]:452-62). The survey included the validated 10-question Mini Z burnout assessment, the results of which were the focus of the new analysis.
The 27% of cardiologists in the burnout group fell into three subcategories, the largest of which comprised those who reported feeling at least one burnout symptom of physical or mental exhaustion. Those who said their burnout symptoms don’t go away and that they think about their work frustrations frequently made up a smaller group. Just a few percent of survey participants fell into the completely burned out category.
Only 51% of the burnout group were satisfied with their financial compensation, compared with 68% of the nonburnout group. Sixty-one percent of the burnout group felt they were treated fairly at their job, as did 86% of the cardiologists who felt burnout. Half of the cardiologists with burnout reported experiencing past discrimination, compared with 37% of the nonburnout group. And 40% of the burnout group felt their family responsibilities hindered career advancement, a sentiment expressed by 22% of the nonburnout group.
EMR “pajama time” cited as a major burden
Two-thirds of cardiologists with constant burnout symptoms or complete burnout cited excessive time spent completing their electronic medical records as a significant contributing factor.
“The electronic medical record ends up taking over our personal time,” according to Dr. Mehta. “We call it ‘pajama time’ because many of us are doing the charts or responding to patients at midnight, on vacation, at meetings like this. There is no separation, and that’s a problem.”
What can be done to reduce burnout
The 2015 Professional Life Survey was the third one in 20 years. Compared with the earlier two, the most recent survey painted a picture of an aging workforce that is less likely to be in private practice. The survey – the first one to assess burnout within the specialty – was carried out by the ACC Women in Cardiology Leadership Council. Armed with the survey results, the ACC leadership is now in the process of redefining the organization’s mission statement to incorporate a new emphasis on providing for physician health and well-being in addition to the more traditional goals of improving the quality and reducing the cost of care.
“Many cardiologists are working a lot harder than they used to, with less personal time. We need to work on mechanisms to reduce burnout by reducing the burdens put on them. The survey data help because they show the cardiology profession, and hopefully hospital administrators, the importance of making a better work environment. That’s the hope,” Dr. Mehta said.
She reported having no financial conflicts of interest regarding the survey.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: There is a noticeable gender gap in U.S. cardiologist burnout.
Data source: This survey of 2,313 U.S. cardiologists addressed burnout and career satisfaction within the profession.
Disclosures: The presenter reported having no financial conflicts of interest regarding the survey, conducted by the American College of Cardiology.
The ‘Virtual Radiology Resident’—Coming to a Computer Near You
Researchers around the world may be able to teach computers how to better detect and diagnose disease, thanks to > 100,000 chest x-ray images and corresponding data recently released by the NIH Clinical Center.
Reading and diagnosing chest x-rays requires careful observation, as well as knowledge of anatomy, physiology, and pathology. When that is combined with the need to consider all common thoracic diseases, it becomes hard to automate a consistent technique for reading images, the NIH says. With the free dataset, the hope is that academic and research institution staff will be able to teach their computers to read and process enormous amounts of scans, to confirm radiologists’ results, and potentially identify anything that may have been overlooked.
The NIH says in addition to being a “virtual radiology resident,” advanced computer technology has other potential benefits: For instance, it could identify slow changes occurring over the course of multiple chest x-rays that might otherwise be overlooked. The technology also would be useful in poor countries that lack radiologists. And in the future, the “resident” might be taught to read more complex images, such as CT and MRI.
The dataset, compiled from scans from > 30,000 patients, including many with advanced lung disease, was scrubbed of private information before release. The images are available via Box at https://nihcc.app.box.com/v/ChestXray-NIHCC.
Researchers around the world may be able to teach computers how to better detect and diagnose disease, thanks to > 100,000 chest x-ray images and corresponding data recently released by the NIH Clinical Center.
Reading and diagnosing chest x-rays requires careful observation, as well as knowledge of anatomy, physiology, and pathology. When that is combined with the need to consider all common thoracic diseases, it becomes hard to automate a consistent technique for reading images, the NIH says. With the free dataset, the hope is that academic and research institution staff will be able to teach their computers to read and process enormous amounts of scans, to confirm radiologists’ results, and potentially identify anything that may have been overlooked.
The NIH says in addition to being a “virtual radiology resident,” advanced computer technology has other potential benefits: For instance, it could identify slow changes occurring over the course of multiple chest x-rays that might otherwise be overlooked. The technology also would be useful in poor countries that lack radiologists. And in the future, the “resident” might be taught to read more complex images, such as CT and MRI.
The dataset, compiled from scans from > 30,000 patients, including many with advanced lung disease, was scrubbed of private information before release. The images are available via Box at https://nihcc.app.box.com/v/ChestXray-NIHCC.
Researchers around the world may be able to teach computers how to better detect and diagnose disease, thanks to > 100,000 chest x-ray images and corresponding data recently released by the NIH Clinical Center.
Reading and diagnosing chest x-rays requires careful observation, as well as knowledge of anatomy, physiology, and pathology. When that is combined with the need to consider all common thoracic diseases, it becomes hard to automate a consistent technique for reading images, the NIH says. With the free dataset, the hope is that academic and research institution staff will be able to teach their computers to read and process enormous amounts of scans, to confirm radiologists’ results, and potentially identify anything that may have been overlooked.
The NIH says in addition to being a “virtual radiology resident,” advanced computer technology has other potential benefits: For instance, it could identify slow changes occurring over the course of multiple chest x-rays that might otherwise be overlooked. The technology also would be useful in poor countries that lack radiologists. And in the future, the “resident” might be taught to read more complex images, such as CT and MRI.
The dataset, compiled from scans from > 30,000 patients, including many with advanced lung disease, was scrubbed of private information before release. The images are available via Box at https://nihcc.app.box.com/v/ChestXray-NIHCC.
Nilotinib approved to treat kids with CML in EU
The European Commission has approved nilotinib (Tasigna®) for the treatment of pediatric patients.
The drug is now approved to treat children age 2 and older with newly diagnosed, Philadelphia chromosome-positive (Ph+), chronic phase (CP) chronic myeloid leukemia (CML) or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
Nilotinib is the only second-generation tyrosine kinase inhibitor currently approved in the European Union (EU) for the treatment of Ph+ CP-CML in children. The approval applies to all EU member states.
According to Novartis, the expanded indication for nilotinib is based on 2 prospective studies of the drug in children with Ph+ CP-CML, which were part of a formal “pediatric investigation plan” agreed upon with the European Medicines Agency.
The company said 69 patients received nilotinib in these studies. The patients ranged in age from 2 to 18. They had either newly diagnosed Ph+ CP-CML or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR.
In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR.
In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.
Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.
The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.
There were no deaths on treatment or after treatment discontinuation. 
The European Commission has approved nilotinib (Tasigna®) for the treatment of pediatric patients.
The drug is now approved to treat children age 2 and older with newly diagnosed, Philadelphia chromosome-positive (Ph+), chronic phase (CP) chronic myeloid leukemia (CML) or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
Nilotinib is the only second-generation tyrosine kinase inhibitor currently approved in the European Union (EU) for the treatment of Ph+ CP-CML in children. The approval applies to all EU member states.
According to Novartis, the expanded indication for nilotinib is based on 2 prospective studies of the drug in children with Ph+ CP-CML, which were part of a formal “pediatric investigation plan” agreed upon with the European Medicines Agency.
The company said 69 patients received nilotinib in these studies. The patients ranged in age from 2 to 18. They had either newly diagnosed Ph+ CP-CML or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR.
In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR.
In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.
Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.
The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.
There were no deaths on treatment or after treatment discontinuation.
The European Commission has approved nilotinib (Tasigna®) for the treatment of pediatric patients.
The drug is now approved to treat children age 2 and older with newly diagnosed, Philadelphia chromosome-positive (Ph+), chronic phase (CP) chronic myeloid leukemia (CML) or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
Nilotinib is the only second-generation tyrosine kinase inhibitor currently approved in the European Union (EU) for the treatment of Ph+ CP-CML in children. The approval applies to all EU member states.
According to Novartis, the expanded indication for nilotinib is based on 2 prospective studies of the drug in children with Ph+ CP-CML, which were part of a formal “pediatric investigation plan” agreed upon with the European Medicines Agency.
The company said 69 patients received nilotinib in these studies. The patients ranged in age from 2 to 18. They had either newly diagnosed Ph+ CP-CML or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR.
In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR.
In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.
Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.
The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.
There were no deaths on treatment or after treatment discontinuation.
CD22-CAR therapy shows activity in rel/ref B-ALL
Researchers say they have reported the first results demonstrating clinical activity of a CD22-directed chimeric antigen receptor (CAR) T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL).
The team conducted a phase 1 study of the therapy in 21 children and adults with relapsed/refractory B-ALL.
Twelve patients achieved a complete response (CR) to the treatment, with 3 patients still in CR at last follow-up.
Sixteen patients developed cytokine release syndrome (CRS), all grade 1 or 2.
Crystal Mackall, MD, of Stanford University in California, and her colleagues reported these results in Nature Medicine.*
“This is the first time that we’ve seen response rates anything like we achieved when we were first testing the CD19 CAR T therapy,” Dr Mackall said.
“We were all a little worried that we wouldn’t find anything comparable, but this study gives hope to the idea that there may be another similar, very potent treatment.”
Patients
Dr Mackall and her colleagues studied the CD22-CAR T-cell therapy in 21 patients with relapsed/refractory B-ALL. They had a median age of 19 (range, 7 to 30).
All of the patients had received a hematopoietic stem cell transplant at least once, and 2 patients had 2 prior transplants each. Seventeen patients had received prior CD19-directed immunotherapy. Fifteen had received CD19-directed CAR T-cell therapy, and 2 had received blinatumomab.
Lymphoblasts were CD19− or CD19dim in 10 patients (9 who had received a CD19-CAR and 1 treated with blinatumomab).
The median CD22 site density was 2839 molecules per cell (range, 613 to 13,452).
Dosing and DLTs
Patients received the CD22-CAR T-cell therapy at 1 of 3 dose levels:
- 0.3 × 106 CD22-CAR T cells per kg body weight (n=6)
- 1 × 106 cells per kg (n=13)
- 3 × 106 cells per kg (n=2).
There was 1 dose-limiting toxicity (DLT) at the first dose level. It was grade 3, self-limited, noninfectious diarrhea that occurred during CRS and resolved with supportive care.
The other DLT occurred in a patient who received treatment at the third dose level. This patient had grade 4 hypoxia that was associated with rapid disease progression. The patient required brief intubation, and the hypoxia was resolved within 24 hours of starting steroid treatment.
Based on these results, the second dose level became the recommended phase 2 dose.
Other adverse events
The researchers said the primary toxicity was CRS, which occurred in 16 patients. Nine patients had grade 1 CRS, and 7 had grade 2.
There were no cases of irreversible neurotoxicity or seizure reported. Among the first 16 patients with complete assessments, there were cases of transient visual hallucinations (n=2), mild unresponsiveness (n=1), mild disorientation (n=1), and mild to moderate pain (n=2). However, these incidents resolved by day 28.
One patient died from gram-negative rod sepsis that developed after the resolution of CRS and neutrophil count recovery to >1000 cells/μL blood. The patient had a history of multi-organ failure due to sepsis.
Response
Twelve patients (57%) had a CR, and 9 of them were minimal residual disease negative.
One CR occurred at the lowest dose of therapy, 1 occurred at the highest dose, and the remaining 10 CRs occurred in patients who received dose level 2.
The researchers said there was no evidence to suggest that previous CD19-directed immunotherapy or diminished surface expression of CD19 impacted response to the CD22-CAR T-cell therapy.
Of the 9 patients who did not respond, 4 progressed and 5 had stable disease.
The researchers said 4 non-responders had “very high disease burden with rapid disease progression.” And 2 non-responders expressed diminished or partial CD22 on leukemic blasts at the time of enrollment.
The median duration of response was 6 months (range, 1.5 to 21+ months). Three patients are still in CR at 6, 9, and 21 months of follow-up.
“The take-home message is that we’ve found another CAR T-cell therapy that displays high-level activity in this phase 1 trial,” Dr Mackall said. “But the relapse rate was also high. So this forces the field to get even more sophisticated. How much of a target is needed for successful, long-lasting treatment? What happens if we target both CD19 and CD22 simultaneously?”
The researchers are already tackling the last question by testing a CAR T-cell therapy that recognizes both CD19 and CD22. They’ve confirmed this therapy can kill cancer cells in vitro and in vivo. Now, they’re testing it in a clinical trial that has opened at Stanford University and will open soon at the National Cancer Institute.
*This research was supported, in part, by the Intramural Research Program, National Cancer Institute and NIH Clinical Center, National Institutes of Health; by a Stand Up to Cancer–St. Baldrick’s Pediatric Dream Team translational research grant; and by a St. Baldrick’s Foundation Scholar Award.
Researchers say they have reported the first results demonstrating clinical activity of a CD22-directed chimeric antigen receptor (CAR) T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL).
The team conducted a phase 1 study of the therapy in 21 children and adults with relapsed/refractory B-ALL.
Twelve patients achieved a complete response (CR) to the treatment, with 3 patients still in CR at last follow-up.
Sixteen patients developed cytokine release syndrome (CRS), all grade 1 or 2.
Crystal Mackall, MD, of Stanford University in California, and her colleagues reported these results in Nature Medicine.*
“This is the first time that we’ve seen response rates anything like we achieved when we were first testing the CD19 CAR T therapy,” Dr Mackall said.
“We were all a little worried that we wouldn’t find anything comparable, but this study gives hope to the idea that there may be another similar, very potent treatment.”
Patients
Dr Mackall and her colleagues studied the CD22-CAR T-cell therapy in 21 patients with relapsed/refractory B-ALL. They had a median age of 19 (range, 7 to 30).
All of the patients had received a hematopoietic stem cell transplant at least once, and 2 patients had 2 prior transplants each. Seventeen patients had received prior CD19-directed immunotherapy. Fifteen had received CD19-directed CAR T-cell therapy, and 2 had received blinatumomab.
Lymphoblasts were CD19− or CD19dim in 10 patients (9 who had received a CD19-CAR and 1 treated with blinatumomab).
The median CD22 site density was 2839 molecules per cell (range, 613 to 13,452).
Dosing and DLTs
Patients received the CD22-CAR T-cell therapy at 1 of 3 dose levels:
- 0.3 × 106 CD22-CAR T cells per kg body weight (n=6)
- 1 × 106 cells per kg (n=13)
- 3 × 106 cells per kg (n=2).
There was 1 dose-limiting toxicity (DLT) at the first dose level. It was grade 3, self-limited, noninfectious diarrhea that occurred during CRS and resolved with supportive care.
The other DLT occurred in a patient who received treatment at the third dose level. This patient had grade 4 hypoxia that was associated with rapid disease progression. The patient required brief intubation, and the hypoxia was resolved within 24 hours of starting steroid treatment.
Based on these results, the second dose level became the recommended phase 2 dose.
Other adverse events
The researchers said the primary toxicity was CRS, which occurred in 16 patients. Nine patients had grade 1 CRS, and 7 had grade 2.
There were no cases of irreversible neurotoxicity or seizure reported. Among the first 16 patients with complete assessments, there were cases of transient visual hallucinations (n=2), mild unresponsiveness (n=1), mild disorientation (n=1), and mild to moderate pain (n=2). However, these incidents resolved by day 28.
One patient died from gram-negative rod sepsis that developed after the resolution of CRS and neutrophil count recovery to >1000 cells/μL blood. The patient had a history of multi-organ failure due to sepsis.
Response
Twelve patients (57%) had a CR, and 9 of them were minimal residual disease negative.
One CR occurred at the lowest dose of therapy, 1 occurred at the highest dose, and the remaining 10 CRs occurred in patients who received dose level 2.
The researchers said there was no evidence to suggest that previous CD19-directed immunotherapy or diminished surface expression of CD19 impacted response to the CD22-CAR T-cell therapy.
Of the 9 patients who did not respond, 4 progressed and 5 had stable disease.
The researchers said 4 non-responders had “very high disease burden with rapid disease progression.” And 2 non-responders expressed diminished or partial CD22 on leukemic blasts at the time of enrollment.
The median duration of response was 6 months (range, 1.5 to 21+ months). Three patients are still in CR at 6, 9, and 21 months of follow-up.
“The take-home message is that we’ve found another CAR T-cell therapy that displays high-level activity in this phase 1 trial,” Dr Mackall said. “But the relapse rate was also high. So this forces the field to get even more sophisticated. How much of a target is needed for successful, long-lasting treatment? What happens if we target both CD19 and CD22 simultaneously?”
The researchers are already tackling the last question by testing a CAR T-cell therapy that recognizes both CD19 and CD22. They’ve confirmed this therapy can kill cancer cells in vitro and in vivo. Now, they’re testing it in a clinical trial that has opened at Stanford University and will open soon at the National Cancer Institute.
*This research was supported, in part, by the Intramural Research Program, National Cancer Institute and NIH Clinical Center, National Institutes of Health; by a Stand Up to Cancer–St. Baldrick’s Pediatric Dream Team translational research grant; and by a St. Baldrick’s Foundation Scholar Award.
Researchers say they have reported the first results demonstrating clinical activity of a CD22-directed chimeric antigen receptor (CAR) T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL).
The team conducted a phase 1 study of the therapy in 21 children and adults with relapsed/refractory B-ALL.
Twelve patients achieved a complete response (CR) to the treatment, with 3 patients still in CR at last follow-up.
Sixteen patients developed cytokine release syndrome (CRS), all grade 1 or 2.
Crystal Mackall, MD, of Stanford University in California, and her colleagues reported these results in Nature Medicine.*
“This is the first time that we’ve seen response rates anything like we achieved when we were first testing the CD19 CAR T therapy,” Dr Mackall said.
“We were all a little worried that we wouldn’t find anything comparable, but this study gives hope to the idea that there may be another similar, very potent treatment.”
Patients
Dr Mackall and her colleagues studied the CD22-CAR T-cell therapy in 21 patients with relapsed/refractory B-ALL. They had a median age of 19 (range, 7 to 30).
All of the patients had received a hematopoietic stem cell transplant at least once, and 2 patients had 2 prior transplants each. Seventeen patients had received prior CD19-directed immunotherapy. Fifteen had received CD19-directed CAR T-cell therapy, and 2 had received blinatumomab.
Lymphoblasts were CD19− or CD19dim in 10 patients (9 who had received a CD19-CAR and 1 treated with blinatumomab).
The median CD22 site density was 2839 molecules per cell (range, 613 to 13,452).
Dosing and DLTs
Patients received the CD22-CAR T-cell therapy at 1 of 3 dose levels:
- 0.3 × 106 CD22-CAR T cells per kg body weight (n=6)
- 1 × 106 cells per kg (n=13)
- 3 × 106 cells per kg (n=2).
There was 1 dose-limiting toxicity (DLT) at the first dose level. It was grade 3, self-limited, noninfectious diarrhea that occurred during CRS and resolved with supportive care.
The other DLT occurred in a patient who received treatment at the third dose level. This patient had grade 4 hypoxia that was associated with rapid disease progression. The patient required brief intubation, and the hypoxia was resolved within 24 hours of starting steroid treatment.
Based on these results, the second dose level became the recommended phase 2 dose.
Other adverse events
The researchers said the primary toxicity was CRS, which occurred in 16 patients. Nine patients had grade 1 CRS, and 7 had grade 2.
There were no cases of irreversible neurotoxicity or seizure reported. Among the first 16 patients with complete assessments, there were cases of transient visual hallucinations (n=2), mild unresponsiveness (n=1), mild disorientation (n=1), and mild to moderate pain (n=2). However, these incidents resolved by day 28.
One patient died from gram-negative rod sepsis that developed after the resolution of CRS and neutrophil count recovery to >1000 cells/μL blood. The patient had a history of multi-organ failure due to sepsis.
Response
Twelve patients (57%) had a CR, and 9 of them were minimal residual disease negative.
One CR occurred at the lowest dose of therapy, 1 occurred at the highest dose, and the remaining 10 CRs occurred in patients who received dose level 2.
The researchers said there was no evidence to suggest that previous CD19-directed immunotherapy or diminished surface expression of CD19 impacted response to the CD22-CAR T-cell therapy.
Of the 9 patients who did not respond, 4 progressed and 5 had stable disease.
The researchers said 4 non-responders had “very high disease burden with rapid disease progression.” And 2 non-responders expressed diminished or partial CD22 on leukemic blasts at the time of enrollment.
The median duration of response was 6 months (range, 1.5 to 21+ months). Three patients are still in CR at 6, 9, and 21 months of follow-up.
“The take-home message is that we’ve found another CAR T-cell therapy that displays high-level activity in this phase 1 trial,” Dr Mackall said. “But the relapse rate was also high. So this forces the field to get even more sophisticated. How much of a target is needed for successful, long-lasting treatment? What happens if we target both CD19 and CD22 simultaneously?”
The researchers are already tackling the last question by testing a CAR T-cell therapy that recognizes both CD19 and CD22. They’ve confirmed this therapy can kill cancer cells in vitro and in vivo. Now, they’re testing it in a clinical trial that has opened at Stanford University and will open soon at the National Cancer Institute.
*This research was supported, in part, by the Intramural Research Program, National Cancer Institute and NIH Clinical Center, National Institutes of Health; by a Stand Up to Cancer–St. Baldrick’s Pediatric Dream Team translational research grant; and by a St. Baldrick’s Foundation Scholar Award.
NOACs may do less harm to kidneys than warfarin
New research suggests warfarin may produce worse renal outcomes than non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation.
In a study of close to 10,000 patients, dabigatran and rivaroxaban were associated with lower risks of adverse renal outcomes than warfarin.
However, risks with warfarin and apixaban were not significantly different.
This research was published in the Journal of the American College of Cardiology.*
“Kidney function decline in patients taking oral anticoagulant drugs is an important topic that has been overlooked in previous clinical trials,” said study author Xiaoxi Yao, PhD, of Mayo Clinic in Rochester, Minnesota.
“Even our past work at Mayo Clinic has been primarily focused on risks for stroke or bleeding.”
For the current study, Dr Yao and her colleagues examined the de-identified records of 9769 patients from the OptumLabs Data Warehouse.
The patients had atrial fibrillation and started taking oral anticoagulants—apixaban, dabigatran, rivaroxaban, or warfarin—between Oct. 1, 2010, and April 30, 2016.
The researchers looked at 4 indicators of kidney function in these patients:
- A 30% or greater decline in estimated glomerular filtration rate (eGFR)
- Doubled serum creatinine level
- Acute kidney injury (AKI)
- Kidney failure.
For the entire study population, the cumulative risk of each event occurring within 2 years of beginning anticoagulation was as follows:
- 24.4% for ≥30% eGFR
- 4.0% for doubled creatinine level
- 14.8% for AKI
- 1.7% for kidney failure.
“Our study demonstrated that renal function decline is very common among atrial fibrillation patients on blood thinners,” Dr Yao said. “About 1 in 4 patients had significantly reduced kidney function within 2 years of being on any of these medications, and 1 in 7 patients had acute kidney injury.”
“In general, patients with atrial fibrillation taking blood-thinning medications tend to have declining kidney function over time,” added study author Peter Noseworthy, MD, of Mayo Clinic in Rochester, Minnesota.
“However, our findings indicate that the non-vitamin K antagonist oral anticoagulants, as a group, are associated with less injury to kidneys than warfarin.”
When the researchers compared all 3 NOACs to warfarin, they found NOAC use was associated with a reduced risk of:
- ≥30% decline in eGFR—hazard ratio (HR)=0.77 (P<0.001)
- Doubling of creatinine—HR=0.62 (P=0.03)
- AKI—HR=0.68 (P<0.001).
However, results differed in one-to-one comparisons.
There was no significant difference between warfarin and apixaban for any of the renal endpoints measured. The HRs (for apixaban vs warfarin) were:
- 0.88 for ≥30% decline in eGFR (P=0.25)
- 0.80 for doubling of creatinine (P=0.51)
- 0.84 for AKI (P=0.16)
- 1.02 for kidney failure (P=0.95).
Dabigatran, on the other hand, was associated with lower risks of ≥30% decline in eGFR and AKI than warfarin. The HRs were as follows:
- 0.72 for ≥30% decline in eGFR (P=0.01)
- 0.64 for doubling of creatinine (P=0.24)
- 0.55 for AKI (P<0.001)
- 0.45 for kidney failure (P=0.21).
Rivaroxaban was associated with lower risks of ≥30% decline in eGFR, doubling of creatinine, and AKI. The HRs were as follows:
- 0.73 for ≥30% decline in eGFR (P<0.001)
- 0.46 for doubling of creatinine (P<0.01)
- 0.69 for AKI (P<0.001)
- 0.63 for kidney failure (P=0.13).
“Patients with atrial fibrillation already face a high risk of kidney disease, perhaps because many such patients have risk factors, such as advanced age, diabetes, and hypertension,” Dr Yao said. “Many drugs these patients are taking rely on kidney function for drug elimination. Therefore, it is particularly important for these patients to choose a drug that minimizes the impact on kidneys.”
“Since non-vitamin K antagonist oral anticoagulants have a different drug mechanism than warfarin, researchers have hypothesized that non-vitamin K antagonist oral anticoagulants may be related to better renal outcomes. Our study is among the first few studies confirming this hypothesis.”
*This study was funded by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, which receives no industry funding. However, study authors did declare industry relationships.
New research suggests warfarin may produce worse renal outcomes than non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation.
In a study of close to 10,000 patients, dabigatran and rivaroxaban were associated with lower risks of adverse renal outcomes than warfarin.
However, risks with warfarin and apixaban were not significantly different.
This research was published in the Journal of the American College of Cardiology.*
“Kidney function decline in patients taking oral anticoagulant drugs is an important topic that has been overlooked in previous clinical trials,” said study author Xiaoxi Yao, PhD, of Mayo Clinic in Rochester, Minnesota.
“Even our past work at Mayo Clinic has been primarily focused on risks for stroke or bleeding.”
For the current study, Dr Yao and her colleagues examined the de-identified records of 9769 patients from the OptumLabs Data Warehouse.
The patients had atrial fibrillation and started taking oral anticoagulants—apixaban, dabigatran, rivaroxaban, or warfarin—between Oct. 1, 2010, and April 30, 2016.
The researchers looked at 4 indicators of kidney function in these patients:
- A 30% or greater decline in estimated glomerular filtration rate (eGFR)
- Doubled serum creatinine level
- Acute kidney injury (AKI)
- Kidney failure.
For the entire study population, the cumulative risk of each event occurring within 2 years of beginning anticoagulation was as follows:
- 24.4% for ≥30% eGFR
- 4.0% for doubled creatinine level
- 14.8% for AKI
- 1.7% for kidney failure.
“Our study demonstrated that renal function decline is very common among atrial fibrillation patients on blood thinners,” Dr Yao said. “About 1 in 4 patients had significantly reduced kidney function within 2 years of being on any of these medications, and 1 in 7 patients had acute kidney injury.”
“In general, patients with atrial fibrillation taking blood-thinning medications tend to have declining kidney function over time,” added study author Peter Noseworthy, MD, of Mayo Clinic in Rochester, Minnesota.
“However, our findings indicate that the non-vitamin K antagonist oral anticoagulants, as a group, are associated with less injury to kidneys than warfarin.”
When the researchers compared all 3 NOACs to warfarin, they found NOAC use was associated with a reduced risk of:
- ≥30% decline in eGFR—hazard ratio (HR)=0.77 (P<0.001)
- Doubling of creatinine—HR=0.62 (P=0.03)
- AKI—HR=0.68 (P<0.001).
However, results differed in one-to-one comparisons.
There was no significant difference between warfarin and apixaban for any of the renal endpoints measured. The HRs (for apixaban vs warfarin) were:
- 0.88 for ≥30% decline in eGFR (P=0.25)
- 0.80 for doubling of creatinine (P=0.51)
- 0.84 for AKI (P=0.16)
- 1.02 for kidney failure (P=0.95).
Dabigatran, on the other hand, was associated with lower risks of ≥30% decline in eGFR and AKI than warfarin. The HRs were as follows:
- 0.72 for ≥30% decline in eGFR (P=0.01)
- 0.64 for doubling of creatinine (P=0.24)
- 0.55 for AKI (P<0.001)
- 0.45 for kidney failure (P=0.21).
Rivaroxaban was associated with lower risks of ≥30% decline in eGFR, doubling of creatinine, and AKI. The HRs were as follows:
- 0.73 for ≥30% decline in eGFR (P<0.001)
- 0.46 for doubling of creatinine (P<0.01)
- 0.69 for AKI (P<0.001)
- 0.63 for kidney failure (P=0.13).
“Patients with atrial fibrillation already face a high risk of kidney disease, perhaps because many such patients have risk factors, such as advanced age, diabetes, and hypertension,” Dr Yao said. “Many drugs these patients are taking rely on kidney function for drug elimination. Therefore, it is particularly important for these patients to choose a drug that minimizes the impact on kidneys.”
“Since non-vitamin K antagonist oral anticoagulants have a different drug mechanism than warfarin, researchers have hypothesized that non-vitamin K antagonist oral anticoagulants may be related to better renal outcomes. Our study is among the first few studies confirming this hypothesis.”
*This study was funded by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, which receives no industry funding. However, study authors did declare industry relationships.
New research suggests warfarin may produce worse renal outcomes than non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation.
In a study of close to 10,000 patients, dabigatran and rivaroxaban were associated with lower risks of adverse renal outcomes than warfarin.
However, risks with warfarin and apixaban were not significantly different.
This research was published in the Journal of the American College of Cardiology.*
“Kidney function decline in patients taking oral anticoagulant drugs is an important topic that has been overlooked in previous clinical trials,” said study author Xiaoxi Yao, PhD, of Mayo Clinic in Rochester, Minnesota.
“Even our past work at Mayo Clinic has been primarily focused on risks for stroke or bleeding.”
For the current study, Dr Yao and her colleagues examined the de-identified records of 9769 patients from the OptumLabs Data Warehouse.
The patients had atrial fibrillation and started taking oral anticoagulants—apixaban, dabigatran, rivaroxaban, or warfarin—between Oct. 1, 2010, and April 30, 2016.
The researchers looked at 4 indicators of kidney function in these patients:
- A 30% or greater decline in estimated glomerular filtration rate (eGFR)
- Doubled serum creatinine level
- Acute kidney injury (AKI)
- Kidney failure.
For the entire study population, the cumulative risk of each event occurring within 2 years of beginning anticoagulation was as follows:
- 24.4% for ≥30% eGFR
- 4.0% for doubled creatinine level
- 14.8% for AKI
- 1.7% for kidney failure.
“Our study demonstrated that renal function decline is very common among atrial fibrillation patients on blood thinners,” Dr Yao said. “About 1 in 4 patients had significantly reduced kidney function within 2 years of being on any of these medications, and 1 in 7 patients had acute kidney injury.”
“In general, patients with atrial fibrillation taking blood-thinning medications tend to have declining kidney function over time,” added study author Peter Noseworthy, MD, of Mayo Clinic in Rochester, Minnesota.
“However, our findings indicate that the non-vitamin K antagonist oral anticoagulants, as a group, are associated with less injury to kidneys than warfarin.”
When the researchers compared all 3 NOACs to warfarin, they found NOAC use was associated with a reduced risk of:
- ≥30% decline in eGFR—hazard ratio (HR)=0.77 (P<0.001)
- Doubling of creatinine—HR=0.62 (P=0.03)
- AKI—HR=0.68 (P<0.001).
However, results differed in one-to-one comparisons.
There was no significant difference between warfarin and apixaban for any of the renal endpoints measured. The HRs (for apixaban vs warfarin) were:
- 0.88 for ≥30% decline in eGFR (P=0.25)
- 0.80 for doubling of creatinine (P=0.51)
- 0.84 for AKI (P=0.16)
- 1.02 for kidney failure (P=0.95).
Dabigatran, on the other hand, was associated with lower risks of ≥30% decline in eGFR and AKI than warfarin. The HRs were as follows:
- 0.72 for ≥30% decline in eGFR (P=0.01)
- 0.64 for doubling of creatinine (P=0.24)
- 0.55 for AKI (P<0.001)
- 0.45 for kidney failure (P=0.21).
Rivaroxaban was associated with lower risks of ≥30% decline in eGFR, doubling of creatinine, and AKI. The HRs were as follows:
- 0.73 for ≥30% decline in eGFR (P<0.001)
- 0.46 for doubling of creatinine (P<0.01)
- 0.69 for AKI (P<0.001)
- 0.63 for kidney failure (P=0.13).
“Patients with atrial fibrillation already face a high risk of kidney disease, perhaps because many such patients have risk factors, such as advanced age, diabetes, and hypertension,” Dr Yao said. “Many drugs these patients are taking rely on kidney function for drug elimination. Therefore, it is particularly important for these patients to choose a drug that minimizes the impact on kidneys.”
“Since non-vitamin K antagonist oral anticoagulants have a different drug mechanism than warfarin, researchers have hypothesized that non-vitamin K antagonist oral anticoagulants may be related to better renal outcomes. Our study is among the first few studies confirming this hypothesis.”
*This study was funded by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, which receives no industry funding. However, study authors did declare industry relationships.
Mixed results for rheumatologists on Medicare quality measures
SAN DIEGO – As quality measures are poised to become crucial to U.S. physician incomes in 2019, an analysis of a nationwide registry sample finds that rheumatologists overall have decent scores on several fronts. But they still need to boost their record on preventive measures that are not geared specifically to their specialty.
“Rheumatologists are performing well, so far, on aspects of care coordination, such as communication with the health care team post osteoporotic fracture and on several patient safety measures, such as avoiding high-risk drugs in the elderly,” said Jinoos Yazdany, MD, of the University of California, San Francisco. However, “in some preventive care measures, such as tobacco screening, there is room for improvement compared to benchmarks that the Centers for Medicare & Medicaid Services has set across providers.”
The ACR created the registry “to help rheumatology harness the power of electronic health record data to advance our understanding of the natural history, treatment, and outcomes of rheumatic disease,” Dr. Yazdany said. “Another important goal was to harness the power of a national registry to measure and improve quality of care and outcomes. Practices can use RISE to see where they are performing well and where there is room for improvement.”
Since 2016, the registry has passively collected data on 2.5 million patients and 13.7 million encounters.
“The quality measures in RISE serve several purposes,” Dr. Yazdany said. “First, they fulfill reporting requirements to CMS through the Merit-Based Incentive Payment System [MIPS]. Second, the measures provide information to practices that can be used to track quality improvement and population health management. Finally, the measures create unprecedented opportunities to learn from practices that are excelling and to adapt successful work flows to improve care for our patients.”
These measures matter. In 2019, payments for many physicians under Medicare Part B will be adjusted based on their performance in these areas in previous years. Most rheumatologists will take part, Dr. Yazdany said.
“Rather than focusing on a single measure, the key number in 2017 for the MIPS program is 70 points across the three domains of Quality, Advancing Care Information, and Improvement Activities,” she said. “Above that threshold, rheumatologists will qualify for an ‘exceptional performance bonus.’ That means they will get a minimum of an additional 0.5% on their Medicare billing.”
She added that “there is no reason that most rheumatologists should not cross the 70-point threshold. Proactively monitoring their progress in RISE will help them succeed.”
The ACR session focused on a registry sample of 225 practices and 750 rheumatologists. The analysis measured their performance from January to September 2017 in the Quality, Advancing Care Information, and Improvement Activities areas.
In terms of meeting benchmarks, the rheumatologists in the sample performed especially well in several areas.
On the drug safety front, across elderly patients, an average of just 3.6% were prescribed one or more high-risk medications, and 0.2% were prescribed two or more.
On rheumatoid arthritis measures, 52% of patients had documentation of tuberculosis screening before biologics, and 46.3% underwent functional status assessments. And in the care coordination and documentation measure, 92.9% documented current medications in the EHR.
Rheumatologists lagged in terms of preventive care, compared with other physicians nationally: The average performance across patients was 77.2% for tobacco screening and counseling, 42.7% for body mass index screening and counseling, and 60.2% for blood pressure management.
Why are these preventive care measures being tracked in rheumatology instead of more rheumatology-specific measures? “CMS requires that physicians submit an outcome measure. Unfortunately, we don’t have validated outcome measures in rheumatology, so we had to adopt outcome measures like controlling blood pressure,” Dr. Yazdany said. “Also, many preventive care measures are designated ‘high priority,’ which enables physicians to get bonus points. We wanted rheumatologists to have access to these extra points and therefore included these measures in RISE.”
The ACR is working on developing outcome measures, she said, “and hopefully we’ll have outcomes to put in the registry in coming years.”
What are the chances that rheumatologists will do well? “Our analyses show that most rheumatologists participating in RISE are well positioned to succeed. If they complete their improvement activities (15% of MIPS), and advancing care information (25% of MIPS) modules, that gets them to 40 points. That means they only need 30 additional points in the quality domain to get to the exceptional performance threshold and qualify for a bonus,” she said. “All 15 of the rheumatologists who have completed all three MIPS categories have reached 70 points, and we anticipate that many others will by the end of the year.”
Even just participating in RISE will boost points, she said. “It is clear that CMS is encouraging the large-scale development of quality improvement registries like RISE.”
In the big picture, she said, “the key point is that rheumatologists should be proactive. They need to understand their performance on measures, pick areas to focus on, including areas where they can easily improve their scores.”
Dr. Yazdany reported no relevant disclosures. The study was funded by ACR.
SAN DIEGO – As quality measures are poised to become crucial to U.S. physician incomes in 2019, an analysis of a nationwide registry sample finds that rheumatologists overall have decent scores on several fronts. But they still need to boost their record on preventive measures that are not geared specifically to their specialty.
“Rheumatologists are performing well, so far, on aspects of care coordination, such as communication with the health care team post osteoporotic fracture and on several patient safety measures, such as avoiding high-risk drugs in the elderly,” said Jinoos Yazdany, MD, of the University of California, San Francisco. However, “in some preventive care measures, such as tobacco screening, there is room for improvement compared to benchmarks that the Centers for Medicare & Medicaid Services has set across providers.”
The ACR created the registry “to help rheumatology harness the power of electronic health record data to advance our understanding of the natural history, treatment, and outcomes of rheumatic disease,” Dr. Yazdany said. “Another important goal was to harness the power of a national registry to measure and improve quality of care and outcomes. Practices can use RISE to see where they are performing well and where there is room for improvement.”
Since 2016, the registry has passively collected data on 2.5 million patients and 13.7 million encounters.
“The quality measures in RISE serve several purposes,” Dr. Yazdany said. “First, they fulfill reporting requirements to CMS through the Merit-Based Incentive Payment System [MIPS]. Second, the measures provide information to practices that can be used to track quality improvement and population health management. Finally, the measures create unprecedented opportunities to learn from practices that are excelling and to adapt successful work flows to improve care for our patients.”
These measures matter. In 2019, payments for many physicians under Medicare Part B will be adjusted based on their performance in these areas in previous years. Most rheumatologists will take part, Dr. Yazdany said.
“Rather than focusing on a single measure, the key number in 2017 for the MIPS program is 70 points across the three domains of Quality, Advancing Care Information, and Improvement Activities,” she said. “Above that threshold, rheumatologists will qualify for an ‘exceptional performance bonus.’ That means they will get a minimum of an additional 0.5% on their Medicare billing.”
She added that “there is no reason that most rheumatologists should not cross the 70-point threshold. Proactively monitoring their progress in RISE will help them succeed.”
The ACR session focused on a registry sample of 225 practices and 750 rheumatologists. The analysis measured their performance from January to September 2017 in the Quality, Advancing Care Information, and Improvement Activities areas.
In terms of meeting benchmarks, the rheumatologists in the sample performed especially well in several areas.
On the drug safety front, across elderly patients, an average of just 3.6% were prescribed one or more high-risk medications, and 0.2% were prescribed two or more.
On rheumatoid arthritis measures, 52% of patients had documentation of tuberculosis screening before biologics, and 46.3% underwent functional status assessments. And in the care coordination and documentation measure, 92.9% documented current medications in the EHR.
Rheumatologists lagged in terms of preventive care, compared with other physicians nationally: The average performance across patients was 77.2% for tobacco screening and counseling, 42.7% for body mass index screening and counseling, and 60.2% for blood pressure management.
Why are these preventive care measures being tracked in rheumatology instead of more rheumatology-specific measures? “CMS requires that physicians submit an outcome measure. Unfortunately, we don’t have validated outcome measures in rheumatology, so we had to adopt outcome measures like controlling blood pressure,” Dr. Yazdany said. “Also, many preventive care measures are designated ‘high priority,’ which enables physicians to get bonus points. We wanted rheumatologists to have access to these extra points and therefore included these measures in RISE.”
The ACR is working on developing outcome measures, she said, “and hopefully we’ll have outcomes to put in the registry in coming years.”
What are the chances that rheumatologists will do well? “Our analyses show that most rheumatologists participating in RISE are well positioned to succeed. If they complete their improvement activities (15% of MIPS), and advancing care information (25% of MIPS) modules, that gets them to 40 points. That means they only need 30 additional points in the quality domain to get to the exceptional performance threshold and qualify for a bonus,” she said. “All 15 of the rheumatologists who have completed all three MIPS categories have reached 70 points, and we anticipate that many others will by the end of the year.”
Even just participating in RISE will boost points, she said. “It is clear that CMS is encouraging the large-scale development of quality improvement registries like RISE.”
In the big picture, she said, “the key point is that rheumatologists should be proactive. They need to understand their performance on measures, pick areas to focus on, including areas where they can easily improve their scores.”
Dr. Yazdany reported no relevant disclosures. The study was funded by ACR.
SAN DIEGO – As quality measures are poised to become crucial to U.S. physician incomes in 2019, an analysis of a nationwide registry sample finds that rheumatologists overall have decent scores on several fronts. But they still need to boost their record on preventive measures that are not geared specifically to their specialty.
“Rheumatologists are performing well, so far, on aspects of care coordination, such as communication with the health care team post osteoporotic fracture and on several patient safety measures, such as avoiding high-risk drugs in the elderly,” said Jinoos Yazdany, MD, of the University of California, San Francisco. However, “in some preventive care measures, such as tobacco screening, there is room for improvement compared to benchmarks that the Centers for Medicare & Medicaid Services has set across providers.”
The ACR created the registry “to help rheumatology harness the power of electronic health record data to advance our understanding of the natural history, treatment, and outcomes of rheumatic disease,” Dr. Yazdany said. “Another important goal was to harness the power of a national registry to measure and improve quality of care and outcomes. Practices can use RISE to see where they are performing well and where there is room for improvement.”
Since 2016, the registry has passively collected data on 2.5 million patients and 13.7 million encounters.
“The quality measures in RISE serve several purposes,” Dr. Yazdany said. “First, they fulfill reporting requirements to CMS through the Merit-Based Incentive Payment System [MIPS]. Second, the measures provide information to practices that can be used to track quality improvement and population health management. Finally, the measures create unprecedented opportunities to learn from practices that are excelling and to adapt successful work flows to improve care for our patients.”
These measures matter. In 2019, payments for many physicians under Medicare Part B will be adjusted based on their performance in these areas in previous years. Most rheumatologists will take part, Dr. Yazdany said.
“Rather than focusing on a single measure, the key number in 2017 for the MIPS program is 70 points across the three domains of Quality, Advancing Care Information, and Improvement Activities,” she said. “Above that threshold, rheumatologists will qualify for an ‘exceptional performance bonus.’ That means they will get a minimum of an additional 0.5% on their Medicare billing.”
She added that “there is no reason that most rheumatologists should not cross the 70-point threshold. Proactively monitoring their progress in RISE will help them succeed.”
The ACR session focused on a registry sample of 225 practices and 750 rheumatologists. The analysis measured their performance from January to September 2017 in the Quality, Advancing Care Information, and Improvement Activities areas.
In terms of meeting benchmarks, the rheumatologists in the sample performed especially well in several areas.
On the drug safety front, across elderly patients, an average of just 3.6% were prescribed one or more high-risk medications, and 0.2% were prescribed two or more.
On rheumatoid arthritis measures, 52% of patients had documentation of tuberculosis screening before biologics, and 46.3% underwent functional status assessments. And in the care coordination and documentation measure, 92.9% documented current medications in the EHR.
Rheumatologists lagged in terms of preventive care, compared with other physicians nationally: The average performance across patients was 77.2% for tobacco screening and counseling, 42.7% for body mass index screening and counseling, and 60.2% for blood pressure management.
Why are these preventive care measures being tracked in rheumatology instead of more rheumatology-specific measures? “CMS requires that physicians submit an outcome measure. Unfortunately, we don’t have validated outcome measures in rheumatology, so we had to adopt outcome measures like controlling blood pressure,” Dr. Yazdany said. “Also, many preventive care measures are designated ‘high priority,’ which enables physicians to get bonus points. We wanted rheumatologists to have access to these extra points and therefore included these measures in RISE.”
The ACR is working on developing outcome measures, she said, “and hopefully we’ll have outcomes to put in the registry in coming years.”
What are the chances that rheumatologists will do well? “Our analyses show that most rheumatologists participating in RISE are well positioned to succeed. If they complete their improvement activities (15% of MIPS), and advancing care information (25% of MIPS) modules, that gets them to 40 points. That means they only need 30 additional points in the quality domain to get to the exceptional performance threshold and qualify for a bonus,” she said. “All 15 of the rheumatologists who have completed all three MIPS categories have reached 70 points, and we anticipate that many others will by the end of the year.”
Even just participating in RISE will boost points, she said. “It is clear that CMS is encouraging the large-scale development of quality improvement registries like RISE.”
In the big picture, she said, “the key point is that rheumatologists should be proactive. They need to understand their performance on measures, pick areas to focus on, including areas where they can easily improve their scores.”
Dr. Yazdany reported no relevant disclosures. The study was funded by ACR.
AT ACR 2017