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CMS pushing primary care with two new payment models
“We’re launching CMS Primary Cares, an initiative of two new payment models that will enroll a quarter or more of traditional Medicare beneficiaries and a quarter of providers in arrangements that pay for keeping patients healthy, rather than ordering procedures,” Alex Azar, secretary of Health and Human Services, said April 22 during a press conference.
“Today’s announcement creates innovation in primary care that has the potential to entirely transform our fee-for-service system – which is about 65% of the Medicare program – into one that drives value,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said during the press conference.
The voluntary models are an array of “new payment options that are all designed to reward [physicians] for keeping people healthy, improving quality of life and delivering positive health outcomes,” Ms. Verma said. “These models are intended to allow clinicians to focus on patient care, not billing, and to do what they’ve been trained to do.”
One option, the Primary Care First model, is aimed at small and solo primary care practices.
The model will “provide participating practices with a predictable payment stream, including a partial cap and some fee-for-service spend,” Ms. Verma said, adding that payments will be adjusted for performance in reducing hospitalizations.
Under Primary Care First, practices will receive a flat payment per beneficiary, allowing clinicians to focus more on care than on revenue cycle management, according to CMS. Practices will be able to receive bonuses of up to 50% or penalties of up to 10%, based on performance, as an incentive to reduce costs and improve quality. Performance will be assessed and paid quarterly. Specifics on the per-beneficiary payment were not released.
Participation in Primary Care First is limited to primary care professionals certified in internal medicine, general medicine, geriatric medicine, family medicine, and hospice and palliative medicine. Practices must provide services to at least 125 Medicare beneficiaries and primary care services must account for at least 70% of billing revenue. Practices also must have experience in value-based payments.
There also will be an option for enhanced payment for caring for patients with chronic illnesses.
“When a patient stays healthy and out of the hospital, these practices will get paid a bonus,” Secretary Azar said. “But if the patient ends up sicker than expected, these practices will bear responsibility for the extra spending up to a certain share of their practices’ revenue.”
More information about participating in the Primary Care First model will be available later in the spring of 2019, with the model launching in 2020.
A second option, the Direct Contracting model is “more ambitious and aimed at larger practices,” Mr. Azar said – those that serve at least 5,000 Medicare beneficiaries.
“Just like in Primary Care First, when patients have a better experience and stay healthier, these practices will make more money,” he continued. “But if patients end up sicker, Direct Contracting Practices will bear the risk for the extra health spending, not just at their own practice, but throughout the system.”
Options under the Direct Contracting model are designed for organizations ready to take on full financial risk that have experience managing large populations with accountable care organizations or working with Medicare Advantage plans, Ms. Verma explained.
The Direct Contracting model will start with two options. The Professional population-based payment (PBP) model offers a lower risk-sharing arrangement (50% savings/losses), while the Global PBP offers a 100% savings/losses risk-sharing arrangement.
CMS also is requesting information on a third payment model, the Geographic PBP model, which would have a similar risk-sharing arrangement as the Global PBP, but participants would assume responsibility for the total cost of care for all Medicare fee-for-service beneficiaries in a defined region.
This model also will launch in 2020.
The new Medicare primary care options were commended by quarters not always supportive of the current government.
Andy Slavitt, CMS administrator under President Obama, voiced his support for the new models.
“There are several watershed moments in the history of the Medicare program, like the coverage of prescription drugs and the shift to paying for better care,” he tweeted April 22. This announcement is “another one as it eases the connection of Medicare beneficiaries to a primary care physician and gives doctors the freedom, rewards, and tools to keep people healthy.”
He continued: “With this great starting point, even as CMS listens to input, physicians and patient groups should be considering who this helps move ... to a healthier country with a more sustainable system.”
The American Medical Association also voiced its support.
“Providing adequate financial support for high-quality primary care must be an essential element of any strategy to improve the quality and affordability of our country’s health care system, Gerald E. Harmon, MD, immediate past chair of the AMA Board of Trustees, said in a statement. “Many primary care physicians have been struggling to deliver the care their patients need and to financially sustain their practices under current Medicare payments. The new primary care payment models announced today will provide practices with more resources and more flexibility to deliver the highest-quality care to their patients.”
The American College of Physicians also noted their support of the new models.
“ACP is optimistic that the new models will emphasize the important role primary care plays in value-based care delivery, that models are voluntary and have a range of risk options, and that practices should use population health management data to reap potential benefits, Robert McLean, MD, ACP president, said in a statement. “ACP is supportive of the fact that the new models aim to reduce administrative burdens – potentially allowing physicians to spend more time with their patients.
“The success and viability of these models will depend on the extent that they are supported by payers in addition to Medicare and Medicaid, are adequately adjusted for differences in the risk and health status of patients seen by each practice, are provided predictable and adequate payments to support and sustain practices (especially smaller independent ones), are appropriately scaled for the financial risk expected of a practice, are provided meaningful and timely data to support improvement, and are truly able to reduce administrative tasks and costs, among other things,” he noted.
As a primary care physician, these new payment models proposed by the Centers for Medicare and Medicaid Services sound like a dream come true. Professional organizations and advocacy groups seem to unanimously agree this is a step in the right direction. Meanwhile, there are a few caveats for primary care docs wondering how much champagne to pop: These models apply to Medicare and some Medicaid contracts. As with any payment reform, the hope is that, if successful, these precedents set by CMS will be adopted by other payers throughout the market and extend to other patients’ plans. It is unclear how this care will be integrated into practices that serve patients with a large payer mix, though it seems to be a natural progression of the Comprehensive Primary Care Plus (CPC+) model practices.
The plans are currently available only in select regions of the United States and in practices that already have the capacity to perform some less traditional care delivery models, which may include home visits, coordination of hospital discharges, telehealth, and group visits.
The measurement of value-based care will likely rely on checkboxes like hemoglobin A1c targets and prescription of statins for secondary prevention of heart disease - measures we already know may be disproportionately more difficult to achieve in the presence of unfavorable “Social Determinants of Health.” The plans account for this by allowing for additional benefit payments for practices caring for “Seriously Ill Patients” or those with “Complex Chronic” conditions. However, it looks like these patients need to be proactively identified when the plans are contracted, and it is unclear who is responsible for determining these designations and how.
Lastly, and most significantly, like the CPC+ models and other similar direct-payment models of care, the practices must agree to carry most - or all - of the financial risk of these patients. Plain and simple, for some, the cost may still be too high.
Sarah G. Candler, MD, MPH, FACP is a primary care physician in Houston.
As a primary care physician, these new payment models proposed by the Centers for Medicare and Medicaid Services sound like a dream come true. Professional organizations and advocacy groups seem to unanimously agree this is a step in the right direction. Meanwhile, there are a few caveats for primary care docs wondering how much champagne to pop: These models apply to Medicare and some Medicaid contracts. As with any payment reform, the hope is that, if successful, these precedents set by CMS will be adopted by other payers throughout the market and extend to other patients’ plans. It is unclear how this care will be integrated into practices that serve patients with a large payer mix, though it seems to be a natural progression of the Comprehensive Primary Care Plus (CPC+) model practices.
The plans are currently available only in select regions of the United States and in practices that already have the capacity to perform some less traditional care delivery models, which may include home visits, coordination of hospital discharges, telehealth, and group visits.
The measurement of value-based care will likely rely on checkboxes like hemoglobin A1c targets and prescription of statins for secondary prevention of heart disease - measures we already know may be disproportionately more difficult to achieve in the presence of unfavorable “Social Determinants of Health.” The plans account for this by allowing for additional benefit payments for practices caring for “Seriously Ill Patients” or those with “Complex Chronic” conditions. However, it looks like these patients need to be proactively identified when the plans are contracted, and it is unclear who is responsible for determining these designations and how.
Lastly, and most significantly, like the CPC+ models and other similar direct-payment models of care, the practices must agree to carry most - or all - of the financial risk of these patients. Plain and simple, for some, the cost may still be too high.
Sarah G. Candler, MD, MPH, FACP is a primary care physician in Houston.
As a primary care physician, these new payment models proposed by the Centers for Medicare and Medicaid Services sound like a dream come true. Professional organizations and advocacy groups seem to unanimously agree this is a step in the right direction. Meanwhile, there are a few caveats for primary care docs wondering how much champagne to pop: These models apply to Medicare and some Medicaid contracts. As with any payment reform, the hope is that, if successful, these precedents set by CMS will be adopted by other payers throughout the market and extend to other patients’ plans. It is unclear how this care will be integrated into practices that serve patients with a large payer mix, though it seems to be a natural progression of the Comprehensive Primary Care Plus (CPC+) model practices.
The plans are currently available only in select regions of the United States and in practices that already have the capacity to perform some less traditional care delivery models, which may include home visits, coordination of hospital discharges, telehealth, and group visits.
The measurement of value-based care will likely rely on checkboxes like hemoglobin A1c targets and prescription of statins for secondary prevention of heart disease - measures we already know may be disproportionately more difficult to achieve in the presence of unfavorable “Social Determinants of Health.” The plans account for this by allowing for additional benefit payments for practices caring for “Seriously Ill Patients” or those with “Complex Chronic” conditions. However, it looks like these patients need to be proactively identified when the plans are contracted, and it is unclear who is responsible for determining these designations and how.
Lastly, and most significantly, like the CPC+ models and other similar direct-payment models of care, the practices must agree to carry most - or all - of the financial risk of these patients. Plain and simple, for some, the cost may still be too high.
Sarah G. Candler, MD, MPH, FACP is a primary care physician in Houston.
“We’re launching CMS Primary Cares, an initiative of two new payment models that will enroll a quarter or more of traditional Medicare beneficiaries and a quarter of providers in arrangements that pay for keeping patients healthy, rather than ordering procedures,” Alex Azar, secretary of Health and Human Services, said April 22 during a press conference.
“Today’s announcement creates innovation in primary care that has the potential to entirely transform our fee-for-service system – which is about 65% of the Medicare program – into one that drives value,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said during the press conference.
The voluntary models are an array of “new payment options that are all designed to reward [physicians] for keeping people healthy, improving quality of life and delivering positive health outcomes,” Ms. Verma said. “These models are intended to allow clinicians to focus on patient care, not billing, and to do what they’ve been trained to do.”
One option, the Primary Care First model, is aimed at small and solo primary care practices.
The model will “provide participating practices with a predictable payment stream, including a partial cap and some fee-for-service spend,” Ms. Verma said, adding that payments will be adjusted for performance in reducing hospitalizations.
Under Primary Care First, practices will receive a flat payment per beneficiary, allowing clinicians to focus more on care than on revenue cycle management, according to CMS. Practices will be able to receive bonuses of up to 50% or penalties of up to 10%, based on performance, as an incentive to reduce costs and improve quality. Performance will be assessed and paid quarterly. Specifics on the per-beneficiary payment were not released.
Participation in Primary Care First is limited to primary care professionals certified in internal medicine, general medicine, geriatric medicine, family medicine, and hospice and palliative medicine. Practices must provide services to at least 125 Medicare beneficiaries and primary care services must account for at least 70% of billing revenue. Practices also must have experience in value-based payments.
There also will be an option for enhanced payment for caring for patients with chronic illnesses.
“When a patient stays healthy and out of the hospital, these practices will get paid a bonus,” Secretary Azar said. “But if the patient ends up sicker than expected, these practices will bear responsibility for the extra spending up to a certain share of their practices’ revenue.”
More information about participating in the Primary Care First model will be available later in the spring of 2019, with the model launching in 2020.
A second option, the Direct Contracting model is “more ambitious and aimed at larger practices,” Mr. Azar said – those that serve at least 5,000 Medicare beneficiaries.
“Just like in Primary Care First, when patients have a better experience and stay healthier, these practices will make more money,” he continued. “But if patients end up sicker, Direct Contracting Practices will bear the risk for the extra health spending, not just at their own practice, but throughout the system.”
Options under the Direct Contracting model are designed for organizations ready to take on full financial risk that have experience managing large populations with accountable care organizations or working with Medicare Advantage plans, Ms. Verma explained.
The Direct Contracting model will start with two options. The Professional population-based payment (PBP) model offers a lower risk-sharing arrangement (50% savings/losses), while the Global PBP offers a 100% savings/losses risk-sharing arrangement.
CMS also is requesting information on a third payment model, the Geographic PBP model, which would have a similar risk-sharing arrangement as the Global PBP, but participants would assume responsibility for the total cost of care for all Medicare fee-for-service beneficiaries in a defined region.
This model also will launch in 2020.
The new Medicare primary care options were commended by quarters not always supportive of the current government.
Andy Slavitt, CMS administrator under President Obama, voiced his support for the new models.
“There are several watershed moments in the history of the Medicare program, like the coverage of prescription drugs and the shift to paying for better care,” he tweeted April 22. This announcement is “another one as it eases the connection of Medicare beneficiaries to a primary care physician and gives doctors the freedom, rewards, and tools to keep people healthy.”
He continued: “With this great starting point, even as CMS listens to input, physicians and patient groups should be considering who this helps move ... to a healthier country with a more sustainable system.”
The American Medical Association also voiced its support.
“Providing adequate financial support for high-quality primary care must be an essential element of any strategy to improve the quality and affordability of our country’s health care system, Gerald E. Harmon, MD, immediate past chair of the AMA Board of Trustees, said in a statement. “Many primary care physicians have been struggling to deliver the care their patients need and to financially sustain their practices under current Medicare payments. The new primary care payment models announced today will provide practices with more resources and more flexibility to deliver the highest-quality care to their patients.”
The American College of Physicians also noted their support of the new models.
“ACP is optimistic that the new models will emphasize the important role primary care plays in value-based care delivery, that models are voluntary and have a range of risk options, and that practices should use population health management data to reap potential benefits, Robert McLean, MD, ACP president, said in a statement. “ACP is supportive of the fact that the new models aim to reduce administrative burdens – potentially allowing physicians to spend more time with their patients.
“The success and viability of these models will depend on the extent that they are supported by payers in addition to Medicare and Medicaid, are adequately adjusted for differences in the risk and health status of patients seen by each practice, are provided predictable and adequate payments to support and sustain practices (especially smaller independent ones), are appropriately scaled for the financial risk expected of a practice, are provided meaningful and timely data to support improvement, and are truly able to reduce administrative tasks and costs, among other things,” he noted.
“We’re launching CMS Primary Cares, an initiative of two new payment models that will enroll a quarter or more of traditional Medicare beneficiaries and a quarter of providers in arrangements that pay for keeping patients healthy, rather than ordering procedures,” Alex Azar, secretary of Health and Human Services, said April 22 during a press conference.
“Today’s announcement creates innovation in primary care that has the potential to entirely transform our fee-for-service system – which is about 65% of the Medicare program – into one that drives value,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said during the press conference.
The voluntary models are an array of “new payment options that are all designed to reward [physicians] for keeping people healthy, improving quality of life and delivering positive health outcomes,” Ms. Verma said. “These models are intended to allow clinicians to focus on patient care, not billing, and to do what they’ve been trained to do.”
One option, the Primary Care First model, is aimed at small and solo primary care practices.
The model will “provide participating practices with a predictable payment stream, including a partial cap and some fee-for-service spend,” Ms. Verma said, adding that payments will be adjusted for performance in reducing hospitalizations.
Under Primary Care First, practices will receive a flat payment per beneficiary, allowing clinicians to focus more on care than on revenue cycle management, according to CMS. Practices will be able to receive bonuses of up to 50% or penalties of up to 10%, based on performance, as an incentive to reduce costs and improve quality. Performance will be assessed and paid quarterly. Specifics on the per-beneficiary payment were not released.
Participation in Primary Care First is limited to primary care professionals certified in internal medicine, general medicine, geriatric medicine, family medicine, and hospice and palliative medicine. Practices must provide services to at least 125 Medicare beneficiaries and primary care services must account for at least 70% of billing revenue. Practices also must have experience in value-based payments.
There also will be an option for enhanced payment for caring for patients with chronic illnesses.
“When a patient stays healthy and out of the hospital, these practices will get paid a bonus,” Secretary Azar said. “But if the patient ends up sicker than expected, these practices will bear responsibility for the extra spending up to a certain share of their practices’ revenue.”
More information about participating in the Primary Care First model will be available later in the spring of 2019, with the model launching in 2020.
A second option, the Direct Contracting model is “more ambitious and aimed at larger practices,” Mr. Azar said – those that serve at least 5,000 Medicare beneficiaries.
“Just like in Primary Care First, when patients have a better experience and stay healthier, these practices will make more money,” he continued. “But if patients end up sicker, Direct Contracting Practices will bear the risk for the extra health spending, not just at their own practice, but throughout the system.”
Options under the Direct Contracting model are designed for organizations ready to take on full financial risk that have experience managing large populations with accountable care organizations or working with Medicare Advantage plans, Ms. Verma explained.
The Direct Contracting model will start with two options. The Professional population-based payment (PBP) model offers a lower risk-sharing arrangement (50% savings/losses), while the Global PBP offers a 100% savings/losses risk-sharing arrangement.
CMS also is requesting information on a third payment model, the Geographic PBP model, which would have a similar risk-sharing arrangement as the Global PBP, but participants would assume responsibility for the total cost of care for all Medicare fee-for-service beneficiaries in a defined region.
This model also will launch in 2020.
The new Medicare primary care options were commended by quarters not always supportive of the current government.
Andy Slavitt, CMS administrator under President Obama, voiced his support for the new models.
“There are several watershed moments in the history of the Medicare program, like the coverage of prescription drugs and the shift to paying for better care,” he tweeted April 22. This announcement is “another one as it eases the connection of Medicare beneficiaries to a primary care physician and gives doctors the freedom, rewards, and tools to keep people healthy.”
He continued: “With this great starting point, even as CMS listens to input, physicians and patient groups should be considering who this helps move ... to a healthier country with a more sustainable system.”
The American Medical Association also voiced its support.
“Providing adequate financial support for high-quality primary care must be an essential element of any strategy to improve the quality and affordability of our country’s health care system, Gerald E. Harmon, MD, immediate past chair of the AMA Board of Trustees, said in a statement. “Many primary care physicians have been struggling to deliver the care their patients need and to financially sustain their practices under current Medicare payments. The new primary care payment models announced today will provide practices with more resources and more flexibility to deliver the highest-quality care to their patients.”
The American College of Physicians also noted their support of the new models.
“ACP is optimistic that the new models will emphasize the important role primary care plays in value-based care delivery, that models are voluntary and have a range of risk options, and that practices should use population health management data to reap potential benefits, Robert McLean, MD, ACP president, said in a statement. “ACP is supportive of the fact that the new models aim to reduce administrative burdens – potentially allowing physicians to spend more time with their patients.
“The success and viability of these models will depend on the extent that they are supported by payers in addition to Medicare and Medicaid, are adequately adjusted for differences in the risk and health status of patients seen by each practice, are provided predictable and adequate payments to support and sustain practices (especially smaller independent ones), are appropriately scaled for the financial risk expected of a practice, are provided meaningful and timely data to support improvement, and are truly able to reduce administrative tasks and costs, among other things,” he noted.
Alvogen issues recall for mislabeled fentanyl patches
Alvogen has issued a voluntary recall of two lots of its Fentanyl Transdermal System 12-mcg/h transdermal patches because of a product mislabeling, according to the Food and Drug Administration.
The recall was issued because a small number of cartons labeled as containing 12-mcg/h patches contained 50-mcg/h patches. The 50-mcg/h patches were labeled as such within the package.
Application of a 50-mcg/h patch instead of a 12-mcg/h patch could result in serious, life-threatening, or fatal respiratory depression. Groups at potential risk for such adverse events include first-time users of the patch, children, and the elderly. No reports of serious adverse events have yet been reported.
“Pharmacies are requested not to dispense any product subject to this recall,” the FDA said in a press release. Patients who “have product subject to this recall should immediately remove any patch currently in use and contact their health care provider. Patients with unused product should return it to point of purchase for replacement.”
Find more information on the recall at the FDA website.
Alvogen has issued a voluntary recall of two lots of its Fentanyl Transdermal System 12-mcg/h transdermal patches because of a product mislabeling, according to the Food and Drug Administration.
The recall was issued because a small number of cartons labeled as containing 12-mcg/h patches contained 50-mcg/h patches. The 50-mcg/h patches were labeled as such within the package.
Application of a 50-mcg/h patch instead of a 12-mcg/h patch could result in serious, life-threatening, or fatal respiratory depression. Groups at potential risk for such adverse events include first-time users of the patch, children, and the elderly. No reports of serious adverse events have yet been reported.
“Pharmacies are requested not to dispense any product subject to this recall,” the FDA said in a press release. Patients who “have product subject to this recall should immediately remove any patch currently in use and contact their health care provider. Patients with unused product should return it to point of purchase for replacement.”
Find more information on the recall at the FDA website.
Alvogen has issued a voluntary recall of two lots of its Fentanyl Transdermal System 12-mcg/h transdermal patches because of a product mislabeling, according to the Food and Drug Administration.
The recall was issued because a small number of cartons labeled as containing 12-mcg/h patches contained 50-mcg/h patches. The 50-mcg/h patches were labeled as such within the package.
Application of a 50-mcg/h patch instead of a 12-mcg/h patch could result in serious, life-threatening, or fatal respiratory depression. Groups at potential risk for such adverse events include first-time users of the patch, children, and the elderly. No reports of serious adverse events have yet been reported.
“Pharmacies are requested not to dispense any product subject to this recall,” the FDA said in a press release. Patients who “have product subject to this recall should immediately remove any patch currently in use and contact their health care provider. Patients with unused product should return it to point of purchase for replacement.”
Find more information on the recall at the FDA website.
MS: Partnering With Patients to Improve Health
Sharon, a 19-year-old woman, has a history of right optic neuritis and paraparesis that occurred 2 years ago. At that time, the diagnosis of multiple sclerosis (MS) was confirmed by a brain MRI and lumbar puncture. She has been taking disease-modifying therapy for 2 years and rarely misses a dose. Lately, however, she has experienced worsening symptoms and feels that her MS is progressing. Her neurologist doesn’t agree; he informs her that a recent MRI shows no changes, and her neurologic examination is within normal limits. At his suggestion, she presents to her primary care provider for an annual check-up.
HISTORY & PHYSICAL EXAM
Sharon’s height is 5 ft 2 in and her weight, 170 lb. Her blood pressure is 140/88 mm Hg and pulse, 80 beats/min and regular. Review of systems is remarkable for fatigue, visual changes when she is overheated, and weight gain of about 50 lb during the past year. Her lungs are clear to percussion and auscultation.
Her current medications include oral disease-modifying therapy, which she takes daily; an oral contraceptive (for regulation of her menstrual cycle; she says she is not sexually active); and an occasional pain reliever for headache.
CLINICAL IMPRESSION
Following history-taking and examination, the clinician notes the following impressions about Sharon’s health status:
Obesity: Examination reveals an overweight female with a BMI of 31.1.
Physical inactivity: As a legal secretary, Sharon sits at her desk most of the day. Her exercise is limited to walking to and from the bus to get to work. She has limited time for social activities due to fatigue. She spends most of her time watching television or visiting her parents.
Heat intolerance: While describing her lifestyle, Sharon notes that she does not participate in outdoor activity due to heat intolerance.
Continue to: Ambulation difficulty
Ambulation difficulty: Sharon’s walking and balance are worse than they were 6 months ago—a problem she relates to her MS, not her increased weight. She walks with a wide-based ataxic gait and transfers with difficulty, using the arms of her chair to stand up.
Poor nutritional habits: Sharon reports an irregular diet with an occasional breakfast, a sandwich for lunch, and a microwavable meal for dinner. Between meals, she snacks on nutrition bars, chocolate, and hot and cold coffee.
Smoking: Sharon smokes 1 pack of cigarettes daily.
Headache: As noted, Sharon reports occasional analgesic use for relief of headache pain.
The clinician’s impression is as follows: relapsing MS treated with disease-modifying therapy; obesity; ambulation difficulty; heat intolerance; sedentary lifestyle; and headache. In addition, the patient has the following risk factors: smoking; suboptimal activity and exercise; and poor nutritional habits.
Continue to: DISCUSSION
DISCUSSION
Sharon has relapsing MS treated with disease-modifying therapy. But she also demonstrates or reports several independent risk factors, including borderline hypertension; obesity; inadequate diet; lack of activity and exercise; and possible lack of insight into her disease.1
The plan of care for Sharon should include a review of her MS disease course. As this is explained, it is important to emphasize how adherence to the care plan will yield positive outcomes from the treatment. For example, the patient should understand that the underlying cause of damage in MS is related to the immune system. Providing this education might involve 1 or 2 sessions with written material, simple graphics, and explanation on how disease-modifying therapies work. Even a simple statement such as
The next step is to review Sharon’s risk factors for worsening MS, along with the impact these have on her general health. This might entail a long discussion focusing on the patient’s diet, minimal activity and exercise, and smoking. Sharon’s provider explained how all 3 factors can contribute to poor general health and have been shown to negatively affect MS. There is a general impression that wellness and neurologic diseases such as MS are disconnected. The clinician must “reconnect” the 2 through encouragement, education, and coaching.
By working closely with the patient and providing the education to help her make informed decisions about her health, the clinician can develop a plan to implement that has the patient’s full support. For a patient like Sharon, this includes
- Dietary modifications to improve nutrition and promote healthy weight loss
- A program of daily walking to improve stamina and support the patient’s weight loss program2
- Smoking cessation, including participation in a local support group of former smokers.3
Continue to: In Sharon's case...
In Sharon’s case, both she and her clinician agreed that it was important to meet regularly to assess progress toward their mutually agreed-upon goals. It is not enough to devise a plan—providers need to support patients in their efforts to improve their health. Meeting regularly can motivate patients to stay on track, and it gives providers an opportunity to address problems or concerns that might interfere with the patient’s progress.
1. Dalgas U, Stenager E. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis? Ther Adv Neurol Disord. 2012;5(2):81-95.
2. Gianfrancesco MA, Barcellos LF. Obesity and multiple sclerosis susceptibility: a review. J Neurol Neuromedicine. 2016:1(7):1-5.
3. Healy BC, Eman A, Guttmann CRG, et al. Smoking and disease progression in multiple sclerosis. Arch Neurol. 2009;66(7):858-864.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina.
June Halper is CEO of the Consortium of Multiple Sclerosis Centers and practices at the MS Center of the New Jersey Medical School, Rutgers University, Newark, and at primary care clinic.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina.
June Halper is CEO of the Consortium of Multiple Sclerosis Centers and practices at the MS Center of the New Jersey Medical School, Rutgers University, Newark, and at primary care clinic.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina.
June Halper is CEO of the Consortium of Multiple Sclerosis Centers and practices at the MS Center of the New Jersey Medical School, Rutgers University, Newark, and at primary care clinic.
Sharon, a 19-year-old woman, has a history of right optic neuritis and paraparesis that occurred 2 years ago. At that time, the diagnosis of multiple sclerosis (MS) was confirmed by a brain MRI and lumbar puncture. She has been taking disease-modifying therapy for 2 years and rarely misses a dose. Lately, however, she has experienced worsening symptoms and feels that her MS is progressing. Her neurologist doesn’t agree; he informs her that a recent MRI shows no changes, and her neurologic examination is within normal limits. At his suggestion, she presents to her primary care provider for an annual check-up.
HISTORY & PHYSICAL EXAM
Sharon’s height is 5 ft 2 in and her weight, 170 lb. Her blood pressure is 140/88 mm Hg and pulse, 80 beats/min and regular. Review of systems is remarkable for fatigue, visual changes when she is overheated, and weight gain of about 50 lb during the past year. Her lungs are clear to percussion and auscultation.
Her current medications include oral disease-modifying therapy, which she takes daily; an oral contraceptive (for regulation of her menstrual cycle; she says she is not sexually active); and an occasional pain reliever for headache.
CLINICAL IMPRESSION
Following history-taking and examination, the clinician notes the following impressions about Sharon’s health status:
Obesity: Examination reveals an overweight female with a BMI of 31.1.
Physical inactivity: As a legal secretary, Sharon sits at her desk most of the day. Her exercise is limited to walking to and from the bus to get to work. She has limited time for social activities due to fatigue. She spends most of her time watching television or visiting her parents.
Heat intolerance: While describing her lifestyle, Sharon notes that she does not participate in outdoor activity due to heat intolerance.
Continue to: Ambulation difficulty
Ambulation difficulty: Sharon’s walking and balance are worse than they were 6 months ago—a problem she relates to her MS, not her increased weight. She walks with a wide-based ataxic gait and transfers with difficulty, using the arms of her chair to stand up.
Poor nutritional habits: Sharon reports an irregular diet with an occasional breakfast, a sandwich for lunch, and a microwavable meal for dinner. Between meals, she snacks on nutrition bars, chocolate, and hot and cold coffee.
Smoking: Sharon smokes 1 pack of cigarettes daily.
Headache: As noted, Sharon reports occasional analgesic use for relief of headache pain.
The clinician’s impression is as follows: relapsing MS treated with disease-modifying therapy; obesity; ambulation difficulty; heat intolerance; sedentary lifestyle; and headache. In addition, the patient has the following risk factors: smoking; suboptimal activity and exercise; and poor nutritional habits.
Continue to: DISCUSSION
DISCUSSION
Sharon has relapsing MS treated with disease-modifying therapy. But she also demonstrates or reports several independent risk factors, including borderline hypertension; obesity; inadequate diet; lack of activity and exercise; and possible lack of insight into her disease.1
The plan of care for Sharon should include a review of her MS disease course. As this is explained, it is important to emphasize how adherence to the care plan will yield positive outcomes from the treatment. For example, the patient should understand that the underlying cause of damage in MS is related to the immune system. Providing this education might involve 1 or 2 sessions with written material, simple graphics, and explanation on how disease-modifying therapies work. Even a simple statement such as
The next step is to review Sharon’s risk factors for worsening MS, along with the impact these have on her general health. This might entail a long discussion focusing on the patient’s diet, minimal activity and exercise, and smoking. Sharon’s provider explained how all 3 factors can contribute to poor general health and have been shown to negatively affect MS. There is a general impression that wellness and neurologic diseases such as MS are disconnected. The clinician must “reconnect” the 2 through encouragement, education, and coaching.
By working closely with the patient and providing the education to help her make informed decisions about her health, the clinician can develop a plan to implement that has the patient’s full support. For a patient like Sharon, this includes
- Dietary modifications to improve nutrition and promote healthy weight loss
- A program of daily walking to improve stamina and support the patient’s weight loss program2
- Smoking cessation, including participation in a local support group of former smokers.3
Continue to: In Sharon's case...
In Sharon’s case, both she and her clinician agreed that it was important to meet regularly to assess progress toward their mutually agreed-upon goals. It is not enough to devise a plan—providers need to support patients in their efforts to improve their health. Meeting regularly can motivate patients to stay on track, and it gives providers an opportunity to address problems or concerns that might interfere with the patient’s progress.
Sharon, a 19-year-old woman, has a history of right optic neuritis and paraparesis that occurred 2 years ago. At that time, the diagnosis of multiple sclerosis (MS) was confirmed by a brain MRI and lumbar puncture. She has been taking disease-modifying therapy for 2 years and rarely misses a dose. Lately, however, she has experienced worsening symptoms and feels that her MS is progressing. Her neurologist doesn’t agree; he informs her that a recent MRI shows no changes, and her neurologic examination is within normal limits. At his suggestion, she presents to her primary care provider for an annual check-up.
HISTORY & PHYSICAL EXAM
Sharon’s height is 5 ft 2 in and her weight, 170 lb. Her blood pressure is 140/88 mm Hg and pulse, 80 beats/min and regular. Review of systems is remarkable for fatigue, visual changes when she is overheated, and weight gain of about 50 lb during the past year. Her lungs are clear to percussion and auscultation.
Her current medications include oral disease-modifying therapy, which she takes daily; an oral contraceptive (for regulation of her menstrual cycle; she says she is not sexually active); and an occasional pain reliever for headache.
CLINICAL IMPRESSION
Following history-taking and examination, the clinician notes the following impressions about Sharon’s health status:
Obesity: Examination reveals an overweight female with a BMI of 31.1.
Physical inactivity: As a legal secretary, Sharon sits at her desk most of the day. Her exercise is limited to walking to and from the bus to get to work. She has limited time for social activities due to fatigue. She spends most of her time watching television or visiting her parents.
Heat intolerance: While describing her lifestyle, Sharon notes that she does not participate in outdoor activity due to heat intolerance.
Continue to: Ambulation difficulty
Ambulation difficulty: Sharon’s walking and balance are worse than they were 6 months ago—a problem she relates to her MS, not her increased weight. She walks with a wide-based ataxic gait and transfers with difficulty, using the arms of her chair to stand up.
Poor nutritional habits: Sharon reports an irregular diet with an occasional breakfast, a sandwich for lunch, and a microwavable meal for dinner. Between meals, she snacks on nutrition bars, chocolate, and hot and cold coffee.
Smoking: Sharon smokes 1 pack of cigarettes daily.
Headache: As noted, Sharon reports occasional analgesic use for relief of headache pain.
The clinician’s impression is as follows: relapsing MS treated with disease-modifying therapy; obesity; ambulation difficulty; heat intolerance; sedentary lifestyle; and headache. In addition, the patient has the following risk factors: smoking; suboptimal activity and exercise; and poor nutritional habits.
Continue to: DISCUSSION
DISCUSSION
Sharon has relapsing MS treated with disease-modifying therapy. But she also demonstrates or reports several independent risk factors, including borderline hypertension; obesity; inadequate diet; lack of activity and exercise; and possible lack of insight into her disease.1
The plan of care for Sharon should include a review of her MS disease course. As this is explained, it is important to emphasize how adherence to the care plan will yield positive outcomes from the treatment. For example, the patient should understand that the underlying cause of damage in MS is related to the immune system. Providing this education might involve 1 or 2 sessions with written material, simple graphics, and explanation on how disease-modifying therapies work. Even a simple statement such as
The next step is to review Sharon’s risk factors for worsening MS, along with the impact these have on her general health. This might entail a long discussion focusing on the patient’s diet, minimal activity and exercise, and smoking. Sharon’s provider explained how all 3 factors can contribute to poor general health and have been shown to negatively affect MS. There is a general impression that wellness and neurologic diseases such as MS are disconnected. The clinician must “reconnect” the 2 through encouragement, education, and coaching.
By working closely with the patient and providing the education to help her make informed decisions about her health, the clinician can develop a plan to implement that has the patient’s full support. For a patient like Sharon, this includes
- Dietary modifications to improve nutrition and promote healthy weight loss
- A program of daily walking to improve stamina and support the patient’s weight loss program2
- Smoking cessation, including participation in a local support group of former smokers.3
Continue to: In Sharon's case...
In Sharon’s case, both she and her clinician agreed that it was important to meet regularly to assess progress toward their mutually agreed-upon goals. It is not enough to devise a plan—providers need to support patients in their efforts to improve their health. Meeting regularly can motivate patients to stay on track, and it gives providers an opportunity to address problems or concerns that might interfere with the patient’s progress.
1. Dalgas U, Stenager E. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis? Ther Adv Neurol Disord. 2012;5(2):81-95.
2. Gianfrancesco MA, Barcellos LF. Obesity and multiple sclerosis susceptibility: a review. J Neurol Neuromedicine. 2016:1(7):1-5.
3. Healy BC, Eman A, Guttmann CRG, et al. Smoking and disease progression in multiple sclerosis. Arch Neurol. 2009;66(7):858-864.
1. Dalgas U, Stenager E. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis? Ther Adv Neurol Disord. 2012;5(2):81-95.
2. Gianfrancesco MA, Barcellos LF. Obesity and multiple sclerosis susceptibility: a review. J Neurol Neuromedicine. 2016:1(7):1-5.
3. Healy BC, Eman A, Guttmann CRG, et al. Smoking and disease progression in multiple sclerosis. Arch Neurol. 2009;66(7):858-864.
Model inspired by Netflix, Amazon may help guide MDS treatment
NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.
The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.
Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.
Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.
The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).
The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:
- DNMT3A and SF3B1
- EZH2 and NK
- ASXL1, TET2, and NK
- STAG2, IDH1/2, and NK
- TP53, del(5q), and CK
- BCOR/BCORL1 and NK
- JAK2, TET2, and NK
- U2AF1, +/– ETV6, and NK
However, only the following two combinations could predict response to lenalidomide:
- DDX41 and NK
- MECOM and KDM6A/B
These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.
Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.
“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.
Dr. Madanat and his colleagues reported having no relevant conflicts of interest.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.
The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.
Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.
Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.
The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).
The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:
- DNMT3A and SF3B1
- EZH2 and NK
- ASXL1, TET2, and NK
- STAG2, IDH1/2, and NK
- TP53, del(5q), and CK
- BCOR/BCORL1 and NK
- JAK2, TET2, and NK
- U2AF1, +/– ETV6, and NK
However, only the following two combinations could predict response to lenalidomide:
- DDX41 and NK
- MECOM and KDM6A/B
These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.
Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.
“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.
Dr. Madanat and his colleagues reported having no relevant conflicts of interest.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.
The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.
Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.
Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.
The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).
The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:
- DNMT3A and SF3B1
- EZH2 and NK
- ASXL1, TET2, and NK
- STAG2, IDH1/2, and NK
- TP53, del(5q), and CK
- BCOR/BCORL1 and NK
- JAK2, TET2, and NK
- U2AF1, +/– ETV6, and NK
However, only the following two combinations could predict response to lenalidomide:
- DDX41 and NK
- MECOM and KDM6A/B
These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.
Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.
“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.
Dr. Madanat and his colleagues reported having no relevant conflicts of interest.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
REPORTING FROM ALF 2019
Text messaging may help patients with schizophrenia
A text messaging–based mobile health (mHealth) intervention that relied on lay health supporters improved medication adherence among rural Chinese patients with schizophrenia by 27%, according to results of a study published in PLoS Medicine.
The researchers developed a mHealth protocol intervention that used text messaging and lay health supporters to help patients with schizophrenia to transition from facility-based care to community-based care. The study randomized 278 community-dwelling villagers with schizophrenia to receive care through a community-based free-medicine program either with or without support from the mHealth intervention. Among the 271 patients successfully followed, medication adherence – the primary outcome – was higher in the mHealth group than it was in the control group (adjusted mean difference, 0.12; 95% confidence interval, 0.03-0.22; P = .013).
The investigators wrote that the treatment gaps for schizophrenia in resource-poor areas remain substantial and that text messaging plus lay health support could form a simple and low-cost means of improving the situation in these settings.
SOURCE: Xu D et al. PLoS Med. 2019 Apr 23. doi: 10.1371/journal.pmed.1002785.
A text messaging–based mobile health (mHealth) intervention that relied on lay health supporters improved medication adherence among rural Chinese patients with schizophrenia by 27%, according to results of a study published in PLoS Medicine.
The researchers developed a mHealth protocol intervention that used text messaging and lay health supporters to help patients with schizophrenia to transition from facility-based care to community-based care. The study randomized 278 community-dwelling villagers with schizophrenia to receive care through a community-based free-medicine program either with or without support from the mHealth intervention. Among the 271 patients successfully followed, medication adherence – the primary outcome – was higher in the mHealth group than it was in the control group (adjusted mean difference, 0.12; 95% confidence interval, 0.03-0.22; P = .013).
The investigators wrote that the treatment gaps for schizophrenia in resource-poor areas remain substantial and that text messaging plus lay health support could form a simple and low-cost means of improving the situation in these settings.
SOURCE: Xu D et al. PLoS Med. 2019 Apr 23. doi: 10.1371/journal.pmed.1002785.
A text messaging–based mobile health (mHealth) intervention that relied on lay health supporters improved medication adherence among rural Chinese patients with schizophrenia by 27%, according to results of a study published in PLoS Medicine.
The researchers developed a mHealth protocol intervention that used text messaging and lay health supporters to help patients with schizophrenia to transition from facility-based care to community-based care. The study randomized 278 community-dwelling villagers with schizophrenia to receive care through a community-based free-medicine program either with or without support from the mHealth intervention. Among the 271 patients successfully followed, medication adherence – the primary outcome – was higher in the mHealth group than it was in the control group (adjusted mean difference, 0.12; 95% confidence interval, 0.03-0.22; P = .013).
The investigators wrote that the treatment gaps for schizophrenia in resource-poor areas remain substantial and that text messaging plus lay health support could form a simple and low-cost means of improving the situation in these settings.
SOURCE: Xu D et al. PLoS Med. 2019 Apr 23. doi: 10.1371/journal.pmed.1002785.
FROM PLOS MEDICINE
Plasma levels of neurofilament light track neurodegeneration in MCI and Alzheimer’s disease
Plasma levels of the axonal protein also correlated with its presence in cerebrospinal fluid, and mirrored the changes in amyloid beta (Abeta) 42, Niklas Mattsson, MD, and colleagues wrote in JAMA Neurology.
“Taken together, these findings suggest that the neurofilament light level is a dynamic biomarker that changes throughout the course of Alzheimer’s disease and is sensitive to progressive neurodegeneration,” wrote Dr. Mattsson of Lund (Sweden) University and his coauthors. “This has important implications, given the unmet need for noninvasive blood-based methods to objectively track longitudinal neurodegeneration in Alzheimer’s disease.”
A blood-based biomarker of Alzheimer’s disease progression could open a new door for drug trials, the authors noted. Previously, NfL levels have only been available by lumbar puncture – a invasive and expensive test that many patients resist. If NfL plasma levels do reliably track dementia progression, the test could become a standard part of clinical trials, providing regular drug response data as the study progresses.
Neurofilaments are polypeptides that give structure to the neuronal cytoskeleton and regulate microtubule function. Injured cells release the protein very quickly. Neurofilaments are elevated in traumatic brain injury, multiple sclerosis, and some psychiatric illnesses. Neurofilament levels have even been used to predict neurologic recovery after cardiac arrest.
Dr. Mattsson and his team used data obtained over 11 years from 1,583 subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative study. The sample comprised three groups: cognitively unimpaired controls (401), patients with MCI (855), and patients with Alzheimer’s dementia (327). The investigators analyzed 4,326 samples.
In addition to the NfL measurements, they tracked Abeta and tau in cerebrospinal fluid (CSF), structural brain changes by 18fluorodeoxyglucose (FDG)–PET and MRI, and cognitive and functional performance. The primary outcome was NfL’s association with these changes. The team set the lower limit of NfL as 6.7 ng/L and the upper, 1,620 ng/L.
At baseline, only advancing age correlated with NfL levels. But it was significantly higher in patients with MCI (37.9 ng/L) and Alzheimer’s dementia (45.9 ng/L) than it was in the control subjects (32.1 ng/L). Over the years of follow-up, levels increased in all groups, but NfL increased more rapidly among patients with MCI and Alzheimer’s dementia than controls (2.7 vs. 2.4 ng/L per year). The difference was most pronounced when comparing levels in patients with Alzheimer’s dementia and MCI with controls. However, control subjects who were Abeta positive by CSF had greater NfL changes than Abeta-negative controls.
Baseline measures of CSF Abeta and tau, as well as hippocampal and ventricular volume and cortical thickness, also correlated with NfL levels, as did cognition and functional scores.
During follow-up, the diagnostic groups showed different NfL trajectories, which correlated strongly with the other measures.
In the control group, NfL increases correlated with lower FDG-PET measures, lower CSF Abeta, reduced hippocampal volume, and higher ventricular volume. Among patients with MCI, NfL increases correlated most strongly with hippocampal volume, temporal region, and cognition. Among patients with Alzheimer’s dementia, the NfL increase most strongly tracked cognitive decline,
When the investigators applied these findings to the A/T/N (amyloid, tau, neurodegeneration) classification system, NfL most often correlated with neurodegeneration, but not always. This might suggest that the neuronal damage occurred separately from Abeta changes. In all three groups, rapid NfL increases mirrored the rate of change in most other measures.
“In controls and patients with MCI and Alzheimer’s dementia, greater rates of NfL were associated with accelerated reduction in FDG-PET measures … expansion of ventricular volume,” and a reduction in cognitive and functional performance, Dr. Mattsson and his colleagues wrote.“ In addition, greater increases in NfL levels were associated with accelerated loss of hippocampal volume and entorhinal cortical thickness in controls and patients with MCI and with accelerated increases in total tau level, phosphorylated tau level, and white matter lesions in patients with MCI. In general, the concentrations of blood-based NfL appears to reflect the intensity of the neuronal injury.”
Dr Mattsson reported being a consultant for the Alzheimer’s Disease Neuroimaging Initiative.
SOURCE: Mattsson N et al. JAMA Neurol. 2019 Apr 22. doi: 10.1001/jamaneurol.2019.0765.
This is an impressive study that convincingly demonstrates the sensitivity of plasma neurofilament light (NfL) to disease progression in patients with mild cognitive impairment and dementia in the Alzheimer’s Disease Neuroimaging Initiative cohort.
It is known that NfL is sensitive to neuronal damage that can result from a variety of pathologies, not limited to Alzheimer’s disease, so it is not diagnostically specific. In the present study there was even overlap of values between the cognitively unimpaired and mild cognitive impairment groups at baseline as well, although the levels separated over time.
In the right setting, NfL might still be a clinically useful diagnostic marker, especially for mild-stage disease when other clinical measures such as mental status scores and structural brain scans are inconclusive, and further study seems warranted for such a possibility.
Its greatest utility, however, will likely be in clinical trials. It would have been of the greatest interest to know how NfL levels changed in the setting of demonstrated cerebral amyloid clearance by agents such as aducanumab that failed to halt dementia progression, or in the setting of BACE1 inhibitor-related worsening of cognition. Did NfL levels remain static in the former and rise in the latter? Looking ahead, it seems likely that this easily accessed biomarker will become an integral part of clinical trial design. Assuming cost is not overly burdensome, it may even find its way eventually into clinical practice.
Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.
This is an impressive study that convincingly demonstrates the sensitivity of plasma neurofilament light (NfL) to disease progression in patients with mild cognitive impairment and dementia in the Alzheimer’s Disease Neuroimaging Initiative cohort.
It is known that NfL is sensitive to neuronal damage that can result from a variety of pathologies, not limited to Alzheimer’s disease, so it is not diagnostically specific. In the present study there was even overlap of values between the cognitively unimpaired and mild cognitive impairment groups at baseline as well, although the levels separated over time.
In the right setting, NfL might still be a clinically useful diagnostic marker, especially for mild-stage disease when other clinical measures such as mental status scores and structural brain scans are inconclusive, and further study seems warranted for such a possibility.
Its greatest utility, however, will likely be in clinical trials. It would have been of the greatest interest to know how NfL levels changed in the setting of demonstrated cerebral amyloid clearance by agents such as aducanumab that failed to halt dementia progression, or in the setting of BACE1 inhibitor-related worsening of cognition. Did NfL levels remain static in the former and rise in the latter? Looking ahead, it seems likely that this easily accessed biomarker will become an integral part of clinical trial design. Assuming cost is not overly burdensome, it may even find its way eventually into clinical practice.
Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.
This is an impressive study that convincingly demonstrates the sensitivity of plasma neurofilament light (NfL) to disease progression in patients with mild cognitive impairment and dementia in the Alzheimer’s Disease Neuroimaging Initiative cohort.
It is known that NfL is sensitive to neuronal damage that can result from a variety of pathologies, not limited to Alzheimer’s disease, so it is not diagnostically specific. In the present study there was even overlap of values between the cognitively unimpaired and mild cognitive impairment groups at baseline as well, although the levels separated over time.
In the right setting, NfL might still be a clinically useful diagnostic marker, especially for mild-stage disease when other clinical measures such as mental status scores and structural brain scans are inconclusive, and further study seems warranted for such a possibility.
Its greatest utility, however, will likely be in clinical trials. It would have been of the greatest interest to know how NfL levels changed in the setting of demonstrated cerebral amyloid clearance by agents such as aducanumab that failed to halt dementia progression, or in the setting of BACE1 inhibitor-related worsening of cognition. Did NfL levels remain static in the former and rise in the latter? Looking ahead, it seems likely that this easily accessed biomarker will become an integral part of clinical trial design. Assuming cost is not overly burdensome, it may even find its way eventually into clinical practice.
Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.
Plasma levels of the axonal protein also correlated with its presence in cerebrospinal fluid, and mirrored the changes in amyloid beta (Abeta) 42, Niklas Mattsson, MD, and colleagues wrote in JAMA Neurology.
“Taken together, these findings suggest that the neurofilament light level is a dynamic biomarker that changes throughout the course of Alzheimer’s disease and is sensitive to progressive neurodegeneration,” wrote Dr. Mattsson of Lund (Sweden) University and his coauthors. “This has important implications, given the unmet need for noninvasive blood-based methods to objectively track longitudinal neurodegeneration in Alzheimer’s disease.”
A blood-based biomarker of Alzheimer’s disease progression could open a new door for drug trials, the authors noted. Previously, NfL levels have only been available by lumbar puncture – a invasive and expensive test that many patients resist. If NfL plasma levels do reliably track dementia progression, the test could become a standard part of clinical trials, providing regular drug response data as the study progresses.
Neurofilaments are polypeptides that give structure to the neuronal cytoskeleton and regulate microtubule function. Injured cells release the protein very quickly. Neurofilaments are elevated in traumatic brain injury, multiple sclerosis, and some psychiatric illnesses. Neurofilament levels have even been used to predict neurologic recovery after cardiac arrest.
Dr. Mattsson and his team used data obtained over 11 years from 1,583 subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative study. The sample comprised three groups: cognitively unimpaired controls (401), patients with MCI (855), and patients with Alzheimer’s dementia (327). The investigators analyzed 4,326 samples.
In addition to the NfL measurements, they tracked Abeta and tau in cerebrospinal fluid (CSF), structural brain changes by 18fluorodeoxyglucose (FDG)–PET and MRI, and cognitive and functional performance. The primary outcome was NfL’s association with these changes. The team set the lower limit of NfL as 6.7 ng/L and the upper, 1,620 ng/L.
At baseline, only advancing age correlated with NfL levels. But it was significantly higher in patients with MCI (37.9 ng/L) and Alzheimer’s dementia (45.9 ng/L) than it was in the control subjects (32.1 ng/L). Over the years of follow-up, levels increased in all groups, but NfL increased more rapidly among patients with MCI and Alzheimer’s dementia than controls (2.7 vs. 2.4 ng/L per year). The difference was most pronounced when comparing levels in patients with Alzheimer’s dementia and MCI with controls. However, control subjects who were Abeta positive by CSF had greater NfL changes than Abeta-negative controls.
Baseline measures of CSF Abeta and tau, as well as hippocampal and ventricular volume and cortical thickness, also correlated with NfL levels, as did cognition and functional scores.
During follow-up, the diagnostic groups showed different NfL trajectories, which correlated strongly with the other measures.
In the control group, NfL increases correlated with lower FDG-PET measures, lower CSF Abeta, reduced hippocampal volume, and higher ventricular volume. Among patients with MCI, NfL increases correlated most strongly with hippocampal volume, temporal region, and cognition. Among patients with Alzheimer’s dementia, the NfL increase most strongly tracked cognitive decline,
When the investigators applied these findings to the A/T/N (amyloid, tau, neurodegeneration) classification system, NfL most often correlated with neurodegeneration, but not always. This might suggest that the neuronal damage occurred separately from Abeta changes. In all three groups, rapid NfL increases mirrored the rate of change in most other measures.
“In controls and patients with MCI and Alzheimer’s dementia, greater rates of NfL were associated with accelerated reduction in FDG-PET measures … expansion of ventricular volume,” and a reduction in cognitive and functional performance, Dr. Mattsson and his colleagues wrote.“ In addition, greater increases in NfL levels were associated with accelerated loss of hippocampal volume and entorhinal cortical thickness in controls and patients with MCI and with accelerated increases in total tau level, phosphorylated tau level, and white matter lesions in patients with MCI. In general, the concentrations of blood-based NfL appears to reflect the intensity of the neuronal injury.”
Dr Mattsson reported being a consultant for the Alzheimer’s Disease Neuroimaging Initiative.
SOURCE: Mattsson N et al. JAMA Neurol. 2019 Apr 22. doi: 10.1001/jamaneurol.2019.0765.
Plasma levels of the axonal protein also correlated with its presence in cerebrospinal fluid, and mirrored the changes in amyloid beta (Abeta) 42, Niklas Mattsson, MD, and colleagues wrote in JAMA Neurology.
“Taken together, these findings suggest that the neurofilament light level is a dynamic biomarker that changes throughout the course of Alzheimer’s disease and is sensitive to progressive neurodegeneration,” wrote Dr. Mattsson of Lund (Sweden) University and his coauthors. “This has important implications, given the unmet need for noninvasive blood-based methods to objectively track longitudinal neurodegeneration in Alzheimer’s disease.”
A blood-based biomarker of Alzheimer’s disease progression could open a new door for drug trials, the authors noted. Previously, NfL levels have only been available by lumbar puncture – a invasive and expensive test that many patients resist. If NfL plasma levels do reliably track dementia progression, the test could become a standard part of clinical trials, providing regular drug response data as the study progresses.
Neurofilaments are polypeptides that give structure to the neuronal cytoskeleton and regulate microtubule function. Injured cells release the protein very quickly. Neurofilaments are elevated in traumatic brain injury, multiple sclerosis, and some psychiatric illnesses. Neurofilament levels have even been used to predict neurologic recovery after cardiac arrest.
Dr. Mattsson and his team used data obtained over 11 years from 1,583 subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative study. The sample comprised three groups: cognitively unimpaired controls (401), patients with MCI (855), and patients with Alzheimer’s dementia (327). The investigators analyzed 4,326 samples.
In addition to the NfL measurements, they tracked Abeta and tau in cerebrospinal fluid (CSF), structural brain changes by 18fluorodeoxyglucose (FDG)–PET and MRI, and cognitive and functional performance. The primary outcome was NfL’s association with these changes. The team set the lower limit of NfL as 6.7 ng/L and the upper, 1,620 ng/L.
At baseline, only advancing age correlated with NfL levels. But it was significantly higher in patients with MCI (37.9 ng/L) and Alzheimer’s dementia (45.9 ng/L) than it was in the control subjects (32.1 ng/L). Over the years of follow-up, levels increased in all groups, but NfL increased more rapidly among patients with MCI and Alzheimer’s dementia than controls (2.7 vs. 2.4 ng/L per year). The difference was most pronounced when comparing levels in patients with Alzheimer’s dementia and MCI with controls. However, control subjects who were Abeta positive by CSF had greater NfL changes than Abeta-negative controls.
Baseline measures of CSF Abeta and tau, as well as hippocampal and ventricular volume and cortical thickness, also correlated with NfL levels, as did cognition and functional scores.
During follow-up, the diagnostic groups showed different NfL trajectories, which correlated strongly with the other measures.
In the control group, NfL increases correlated with lower FDG-PET measures, lower CSF Abeta, reduced hippocampal volume, and higher ventricular volume. Among patients with MCI, NfL increases correlated most strongly with hippocampal volume, temporal region, and cognition. Among patients with Alzheimer’s dementia, the NfL increase most strongly tracked cognitive decline,
When the investigators applied these findings to the A/T/N (amyloid, tau, neurodegeneration) classification system, NfL most often correlated with neurodegeneration, but not always. This might suggest that the neuronal damage occurred separately from Abeta changes. In all three groups, rapid NfL increases mirrored the rate of change in most other measures.
“In controls and patients with MCI and Alzheimer’s dementia, greater rates of NfL were associated with accelerated reduction in FDG-PET measures … expansion of ventricular volume,” and a reduction in cognitive and functional performance, Dr. Mattsson and his colleagues wrote.“ In addition, greater increases in NfL levels were associated with accelerated loss of hippocampal volume and entorhinal cortical thickness in controls and patients with MCI and with accelerated increases in total tau level, phosphorylated tau level, and white matter lesions in patients with MCI. In general, the concentrations of blood-based NfL appears to reflect the intensity of the neuronal injury.”
Dr Mattsson reported being a consultant for the Alzheimer’s Disease Neuroimaging Initiative.
SOURCE: Mattsson N et al. JAMA Neurol. 2019 Apr 22. doi: 10.1001/jamaneurol.2019.0765.
FROM JAMA NEUROLOGY
Studies begin to pinpoint ways to diagnose SLE earlier
SAN FRANCISCO – A host of novel clinical and serologic findings that physicians can put to good use right now in helping to distinguish early SLE from its many mimickers have been identified in a large study conducted on four continents, Marta Mosca, MD, PhD, observed at an international congress on systemic lupus erythematosus.
These useful findings aren’t incorporated into the current American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) lupus classification criteria, which have come under criticism for limited sensitivity in identifying early SLE. Some of the novel findings provide support for increased suspicion of early SLE, while others suggest a need to veer in another direction and assess a patient for a disease other than lupus. The study has served to provide input for the proposed new ACR/EULAR weighted SLE classification criteria, although that scheme is meant to be used only for research and not in clinical practice, explained Dr. Mosca of the University of Pisa (Italy).
She was lead author of the four-continent study, which included 616 patients referred to experienced academic lupus centers for possible SLE with a symptom duration of less than 1 year. During up to 3 years of follow-up, 389 patients were diagnosed as having SLE by experienced rheumatologists based upon their clinical judgment, without any requirement to meet the full ACR or SLICC classification criteria. The other 227 patients were determined to be SLE mimickers with conditions including lymphoma, Sjögren’s syndrome, systemic sclerosis, interstitial lung disease, fibromyalgia, antinuclear antibody–positive thyroiditis, and undifferentiated connective tissue disease.
Dr. Mosca also highlighted key recent work by other investigators aimed at speeding the diagnosis of SLE and shortening the duration of what she called “the gray zone” of diagnostic uncertainty, when autoantibodies and insidious symptoms are present but not yet sufficient to make the diagnosis of SLE by conventional criteria. It’s well established that 60%-70% of patients with mild undifferentiated connective tissue disease will remain stable without evolving into SLE during long years of follow-up.
The ultimate objective of all this work is to try to change the natural history of the disease through targeted early aggressive therapy aimed at minimizing the extent of active disease and preventing severe organ involvement.
Among the key takeaways from the four-continent study led by Dr. Mosca: Fever not related to infection was far more prevalent in early SLE than in mimicking conditions, by a margin of 34.5% versus 13.7%. On the other hand, Raynaud’s phenomenon was more than twice as prevalent among patients with mimicking conditions: 22.1% in early SLE, compared with 48.5% in SLE mimickers. Sicca symptoms were present in just 4.4% of early SLE patients versus 34.4% of SLE mimickers. Only 0.3% of early SLE patients complained of dysphagia; the rate was 20-fold higher in the SLE mimickers. Rashes atypical for lupus were twice as frequent in the SLE mimicking conditions (Arthritis Rheumatol. 2019 Jan;71[1]:91-8).
Turning to key differentiating serologic findings, Dr. Mosca noted that anti-double stranded DNA (anti-dsDNA) and anti-Sm antibodies were present in 71.7% and 30.2% of early SLE patients, respectively, compared with 6.9% and 2.6% of SLE mimickers. Anticardiolipin IgM, a positive Coombs test, anti-beta2 glycoprotein-I antibodies, leukopenia, autoimmune hemolytic anemia, and hypocomplementemia were all significantly more common in the early SLE cohort.
In contrast, antibodies to Ro (SS-A) and La (SS-B) were of no value in separating early SLE from its mimickers, according to Dr. Mosca.
Other tipoffs to early SLE
Two separate teams of British researchers have advanced the field in a highly practical way. One group showed in a study of 1,739 newly diagnosed SLE patients and 6,956 controls that in the 5 years prior to diagnosis, the SLE group averaged 9.2 primary care visits per year, compared with 3.8 for controls. The visits clustered around nonspecific complaints of arthritis and arthralgias, alopecia, and rash (Arthritis Care Res. 2017 Jun;69[6]:833-41).
“An accumulating number of primary care office visits and referrals over time should raise suspicion,” Dr. Mosca said.
Other investigators, working with 1,426 cases of newly diagnosed SLE in the U.K. Clinical Practice Research Database, observed that the proportion of patients with disease manifestations in three or more British Isles Lupus Activity Group (BILAG) symptom domains rose from 18.7% at 3 years prior to diagnosis to 39.7% in the year before diagnosis (Lupus Sci Med. 2017 Feb 10;4[1]:e000172. doi: 10.1136/lupus-2016-000172).
“These patients accrue clinical manifestations. It’s not just one symptom, it’s more of a state of being unwell. This is a suspicious factor for the development of lupus,” she continued.
And just as patients who will eventually be diagnosed with SLE accrue a growing number of signs and symptoms during the run up to diagnosis, they also accrue multiple autoantibodies. Moreover, as demonstrated by a multicenter group of U.S. investigators, patients also develop elevated levels of multiple soluble inflammatory markers more than 3.5 years prior to diagnosis of SLE. These include interleukins-5 and -6 and interferon-gamma. And less than 10 months prior to being classified as having SLE, patients develop significantly higher levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand known as APRIL. The investigators developed a predictive model incorporating IL-5, -6, and interferon-gamma levels with antinuclear antibody status that identified future SLE patients with 84% accuracy more than 3.5 years before diagnosis. This could prove useful in selecting high-risk patients for clinical prevention trials (J Autoimmun. 2016 Nov;74:182-93).
Researchers at the University of Leeds (England) have also zeroed in on interferon activity as playing a key role in progression from asymptomatic antinuclear antigen positivity, which is present in up to 25% of the general population, to symptomatic autoimmune connective tissue disease, which affects less than 1%. A multivariate logistic regression analysis identified two independent predictors of development of autoimmune connective tissue disease within the next 12 months: a family history of autoimmune rheumatic disease, which was associated with an 8.2-fold increased risk; and positivity for a pattern of interferon-stimulated gene activity they call IFN-Score-B (Ann Rheum Dis. 2018 Oct;77[10]:1432-9).
All of this work has led up to what Dr. Mosca called “a glance into the future”: the National Institutes of Health–supported Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE), which is now recruiting patients. This randomized, double-blind, placebo-controlled multicenter U.S. trial involves patients who are antinuclear antibody positive at a titer of 1:80 or more plus one or two additional criteria from the SLICC classification scheme. Participants are being randomized to 96 weeks of hydroxychloroquine or placebo. The goal is to learn whether hydroxychloroquine can slow disease progression, with the primary endpoint being the number of SLICC criteria met at the study’s end. The trial will also scrutinize potential biomarkers that could be used to guide treatment decisions (Trials. 2018 Dec 20;19[1]:694. doi: 10.1186/s13063-018-3076-7).
Dr. Mosca reported serving as an adviser to UCB and Lilly.
SAN FRANCISCO – A host of novel clinical and serologic findings that physicians can put to good use right now in helping to distinguish early SLE from its many mimickers have been identified in a large study conducted on four continents, Marta Mosca, MD, PhD, observed at an international congress on systemic lupus erythematosus.
These useful findings aren’t incorporated into the current American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) lupus classification criteria, which have come under criticism for limited sensitivity in identifying early SLE. Some of the novel findings provide support for increased suspicion of early SLE, while others suggest a need to veer in another direction and assess a patient for a disease other than lupus. The study has served to provide input for the proposed new ACR/EULAR weighted SLE classification criteria, although that scheme is meant to be used only for research and not in clinical practice, explained Dr. Mosca of the University of Pisa (Italy).
She was lead author of the four-continent study, which included 616 patients referred to experienced academic lupus centers for possible SLE with a symptom duration of less than 1 year. During up to 3 years of follow-up, 389 patients were diagnosed as having SLE by experienced rheumatologists based upon their clinical judgment, without any requirement to meet the full ACR or SLICC classification criteria. The other 227 patients were determined to be SLE mimickers with conditions including lymphoma, Sjögren’s syndrome, systemic sclerosis, interstitial lung disease, fibromyalgia, antinuclear antibody–positive thyroiditis, and undifferentiated connective tissue disease.
Dr. Mosca also highlighted key recent work by other investigators aimed at speeding the diagnosis of SLE and shortening the duration of what she called “the gray zone” of diagnostic uncertainty, when autoantibodies and insidious symptoms are present but not yet sufficient to make the diagnosis of SLE by conventional criteria. It’s well established that 60%-70% of patients with mild undifferentiated connective tissue disease will remain stable without evolving into SLE during long years of follow-up.
The ultimate objective of all this work is to try to change the natural history of the disease through targeted early aggressive therapy aimed at minimizing the extent of active disease and preventing severe organ involvement.
Among the key takeaways from the four-continent study led by Dr. Mosca: Fever not related to infection was far more prevalent in early SLE than in mimicking conditions, by a margin of 34.5% versus 13.7%. On the other hand, Raynaud’s phenomenon was more than twice as prevalent among patients with mimicking conditions: 22.1% in early SLE, compared with 48.5% in SLE mimickers. Sicca symptoms were present in just 4.4% of early SLE patients versus 34.4% of SLE mimickers. Only 0.3% of early SLE patients complained of dysphagia; the rate was 20-fold higher in the SLE mimickers. Rashes atypical for lupus were twice as frequent in the SLE mimicking conditions (Arthritis Rheumatol. 2019 Jan;71[1]:91-8).
Turning to key differentiating serologic findings, Dr. Mosca noted that anti-double stranded DNA (anti-dsDNA) and anti-Sm antibodies were present in 71.7% and 30.2% of early SLE patients, respectively, compared with 6.9% and 2.6% of SLE mimickers. Anticardiolipin IgM, a positive Coombs test, anti-beta2 glycoprotein-I antibodies, leukopenia, autoimmune hemolytic anemia, and hypocomplementemia were all significantly more common in the early SLE cohort.
In contrast, antibodies to Ro (SS-A) and La (SS-B) were of no value in separating early SLE from its mimickers, according to Dr. Mosca.
Other tipoffs to early SLE
Two separate teams of British researchers have advanced the field in a highly practical way. One group showed in a study of 1,739 newly diagnosed SLE patients and 6,956 controls that in the 5 years prior to diagnosis, the SLE group averaged 9.2 primary care visits per year, compared with 3.8 for controls. The visits clustered around nonspecific complaints of arthritis and arthralgias, alopecia, and rash (Arthritis Care Res. 2017 Jun;69[6]:833-41).
“An accumulating number of primary care office visits and referrals over time should raise suspicion,” Dr. Mosca said.
Other investigators, working with 1,426 cases of newly diagnosed SLE in the U.K. Clinical Practice Research Database, observed that the proportion of patients with disease manifestations in three or more British Isles Lupus Activity Group (BILAG) symptom domains rose from 18.7% at 3 years prior to diagnosis to 39.7% in the year before diagnosis (Lupus Sci Med. 2017 Feb 10;4[1]:e000172. doi: 10.1136/lupus-2016-000172).
“These patients accrue clinical manifestations. It’s not just one symptom, it’s more of a state of being unwell. This is a suspicious factor for the development of lupus,” she continued.
And just as patients who will eventually be diagnosed with SLE accrue a growing number of signs and symptoms during the run up to diagnosis, they also accrue multiple autoantibodies. Moreover, as demonstrated by a multicenter group of U.S. investigators, patients also develop elevated levels of multiple soluble inflammatory markers more than 3.5 years prior to diagnosis of SLE. These include interleukins-5 and -6 and interferon-gamma. And less than 10 months prior to being classified as having SLE, patients develop significantly higher levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand known as APRIL. The investigators developed a predictive model incorporating IL-5, -6, and interferon-gamma levels with antinuclear antibody status that identified future SLE patients with 84% accuracy more than 3.5 years before diagnosis. This could prove useful in selecting high-risk patients for clinical prevention trials (J Autoimmun. 2016 Nov;74:182-93).
Researchers at the University of Leeds (England) have also zeroed in on interferon activity as playing a key role in progression from asymptomatic antinuclear antigen positivity, which is present in up to 25% of the general population, to symptomatic autoimmune connective tissue disease, which affects less than 1%. A multivariate logistic regression analysis identified two independent predictors of development of autoimmune connective tissue disease within the next 12 months: a family history of autoimmune rheumatic disease, which was associated with an 8.2-fold increased risk; and positivity for a pattern of interferon-stimulated gene activity they call IFN-Score-B (Ann Rheum Dis. 2018 Oct;77[10]:1432-9).
All of this work has led up to what Dr. Mosca called “a glance into the future”: the National Institutes of Health–supported Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE), which is now recruiting patients. This randomized, double-blind, placebo-controlled multicenter U.S. trial involves patients who are antinuclear antibody positive at a titer of 1:80 or more plus one or two additional criteria from the SLICC classification scheme. Participants are being randomized to 96 weeks of hydroxychloroquine or placebo. The goal is to learn whether hydroxychloroquine can slow disease progression, with the primary endpoint being the number of SLICC criteria met at the study’s end. The trial will also scrutinize potential biomarkers that could be used to guide treatment decisions (Trials. 2018 Dec 20;19[1]:694. doi: 10.1186/s13063-018-3076-7).
Dr. Mosca reported serving as an adviser to UCB and Lilly.
SAN FRANCISCO – A host of novel clinical and serologic findings that physicians can put to good use right now in helping to distinguish early SLE from its many mimickers have been identified in a large study conducted on four continents, Marta Mosca, MD, PhD, observed at an international congress on systemic lupus erythematosus.
These useful findings aren’t incorporated into the current American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) lupus classification criteria, which have come under criticism for limited sensitivity in identifying early SLE. Some of the novel findings provide support for increased suspicion of early SLE, while others suggest a need to veer in another direction and assess a patient for a disease other than lupus. The study has served to provide input for the proposed new ACR/EULAR weighted SLE classification criteria, although that scheme is meant to be used only for research and not in clinical practice, explained Dr. Mosca of the University of Pisa (Italy).
She was lead author of the four-continent study, which included 616 patients referred to experienced academic lupus centers for possible SLE with a symptom duration of less than 1 year. During up to 3 years of follow-up, 389 patients were diagnosed as having SLE by experienced rheumatologists based upon their clinical judgment, without any requirement to meet the full ACR or SLICC classification criteria. The other 227 patients were determined to be SLE mimickers with conditions including lymphoma, Sjögren’s syndrome, systemic sclerosis, interstitial lung disease, fibromyalgia, antinuclear antibody–positive thyroiditis, and undifferentiated connective tissue disease.
Dr. Mosca also highlighted key recent work by other investigators aimed at speeding the diagnosis of SLE and shortening the duration of what she called “the gray zone” of diagnostic uncertainty, when autoantibodies and insidious symptoms are present but not yet sufficient to make the diagnosis of SLE by conventional criteria. It’s well established that 60%-70% of patients with mild undifferentiated connective tissue disease will remain stable without evolving into SLE during long years of follow-up.
The ultimate objective of all this work is to try to change the natural history of the disease through targeted early aggressive therapy aimed at minimizing the extent of active disease and preventing severe organ involvement.
Among the key takeaways from the four-continent study led by Dr. Mosca: Fever not related to infection was far more prevalent in early SLE than in mimicking conditions, by a margin of 34.5% versus 13.7%. On the other hand, Raynaud’s phenomenon was more than twice as prevalent among patients with mimicking conditions: 22.1% in early SLE, compared with 48.5% in SLE mimickers. Sicca symptoms were present in just 4.4% of early SLE patients versus 34.4% of SLE mimickers. Only 0.3% of early SLE patients complained of dysphagia; the rate was 20-fold higher in the SLE mimickers. Rashes atypical for lupus were twice as frequent in the SLE mimicking conditions (Arthritis Rheumatol. 2019 Jan;71[1]:91-8).
Turning to key differentiating serologic findings, Dr. Mosca noted that anti-double stranded DNA (anti-dsDNA) and anti-Sm antibodies were present in 71.7% and 30.2% of early SLE patients, respectively, compared with 6.9% and 2.6% of SLE mimickers. Anticardiolipin IgM, a positive Coombs test, anti-beta2 glycoprotein-I antibodies, leukopenia, autoimmune hemolytic anemia, and hypocomplementemia were all significantly more common in the early SLE cohort.
In contrast, antibodies to Ro (SS-A) and La (SS-B) were of no value in separating early SLE from its mimickers, according to Dr. Mosca.
Other tipoffs to early SLE
Two separate teams of British researchers have advanced the field in a highly practical way. One group showed in a study of 1,739 newly diagnosed SLE patients and 6,956 controls that in the 5 years prior to diagnosis, the SLE group averaged 9.2 primary care visits per year, compared with 3.8 for controls. The visits clustered around nonspecific complaints of arthritis and arthralgias, alopecia, and rash (Arthritis Care Res. 2017 Jun;69[6]:833-41).
“An accumulating number of primary care office visits and referrals over time should raise suspicion,” Dr. Mosca said.
Other investigators, working with 1,426 cases of newly diagnosed SLE in the U.K. Clinical Practice Research Database, observed that the proportion of patients with disease manifestations in three or more British Isles Lupus Activity Group (BILAG) symptom domains rose from 18.7% at 3 years prior to diagnosis to 39.7% in the year before diagnosis (Lupus Sci Med. 2017 Feb 10;4[1]:e000172. doi: 10.1136/lupus-2016-000172).
“These patients accrue clinical manifestations. It’s not just one symptom, it’s more of a state of being unwell. This is a suspicious factor for the development of lupus,” she continued.
And just as patients who will eventually be diagnosed with SLE accrue a growing number of signs and symptoms during the run up to diagnosis, they also accrue multiple autoantibodies. Moreover, as demonstrated by a multicenter group of U.S. investigators, patients also develop elevated levels of multiple soluble inflammatory markers more than 3.5 years prior to diagnosis of SLE. These include interleukins-5 and -6 and interferon-gamma. And less than 10 months prior to being classified as having SLE, patients develop significantly higher levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand known as APRIL. The investigators developed a predictive model incorporating IL-5, -6, and interferon-gamma levels with antinuclear antibody status that identified future SLE patients with 84% accuracy more than 3.5 years before diagnosis. This could prove useful in selecting high-risk patients for clinical prevention trials (J Autoimmun. 2016 Nov;74:182-93).
Researchers at the University of Leeds (England) have also zeroed in on interferon activity as playing a key role in progression from asymptomatic antinuclear antigen positivity, which is present in up to 25% of the general population, to symptomatic autoimmune connective tissue disease, which affects less than 1%. A multivariate logistic regression analysis identified two independent predictors of development of autoimmune connective tissue disease within the next 12 months: a family history of autoimmune rheumatic disease, which was associated with an 8.2-fold increased risk; and positivity for a pattern of interferon-stimulated gene activity they call IFN-Score-B (Ann Rheum Dis. 2018 Oct;77[10]:1432-9).
All of this work has led up to what Dr. Mosca called “a glance into the future”: the National Institutes of Health–supported Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE), which is now recruiting patients. This randomized, double-blind, placebo-controlled multicenter U.S. trial involves patients who are antinuclear antibody positive at a titer of 1:80 or more plus one or two additional criteria from the SLICC classification scheme. Participants are being randomized to 96 weeks of hydroxychloroquine or placebo. The goal is to learn whether hydroxychloroquine can slow disease progression, with the primary endpoint being the number of SLICC criteria met at the study’s end. The trial will also scrutinize potential biomarkers that could be used to guide treatment decisions (Trials. 2018 Dec 20;19[1]:694. doi: 10.1186/s13063-018-3076-7).
Dr. Mosca reported serving as an adviser to UCB and Lilly.
REPORTING FROM LUPUS 2019
PACIFIC: Patient-reported outcomes unaffected by PD-L1 expression
GENEVA – Level of programmed death-ligand 1 (PD-L1) expression does not impact patient-reported outcomes (PROs) among those receiving durvalumab for stage III non–small cell lung cancer (NSCLC), according to a retrospective analysis of the phase III PACIFIC trial.
The findings support durvalumab for all comers regardless of PD-L1 expression, reported lead author Marina Garassino, MD, of Fondazione IRCCS – Instituto Nazionale dei Tumori in Milan, who presented findings at the European Lung Cancer Congress.
The PACIFIC trial involved 713 patients with stage III NSCLC who did not progress after platinum-based concurrent chemoradiotherapy, demonstrating both improved progression-free and overall survival. Patients were randomized 2:1 to receive either durvalumab (10 mg/kg) or placebo IV every 2 weeks for up to 1 year. Out of 713 patients involved in the trial, 63% had PD-L1 tumor expression level data available for the present analysis, allowing for subgrouping into five categories: expression level of at least 25%, less than 25%, at least 1%, less than 1%, or unknown. The investigators compared PROs from these cohorts using the European Organisation for Research and Treatment of Cancer core quality of life questionnaire and lung cancer module (EORTC QLQ-C30 and -LC13). With scores ranging from 1 to 100 points, clinically meaningful differences were defined by score changes exceeding 10 points. Changes during treatment, from baseline to week 48, were analyzed by a mixed model for repeated measures, overall responses for improvement rates by logistic regression, and hazard ratios for time to deterioration (TTD) by a stratified Cox proportional-hazards model.
The investigators found that most PROs remained consistent over time, without clinically meaningful variations between PD-L1 expression levels. However, as with the entire PACIFIC treatment population, patients in the present analysis showed changes in some PROs. At the meeting presented by the European Society for Medical Oncology, Dr. Garassino noted that it would be unrealistic to describe all PRO comparisons; instead, she presented several examples. For one, in patients receiving durvalumab, dysphagia and alopecia improved in four out of five PD-L1 subgroups and all subgroups, respectively, while patients in the placebo arm reported improvements in both measures regardless of PD-L1 expression. Other improvements tended to favor the durvalumab group; for instance, compared with other subgroups, patients with PD-L1 expression of at least 25% were more likely to report improved chest pain, physical functioning, pain, emotional functioning, and hemoptysis. In contrast, patients receiving placebo with PD-L1 expression less than 25% were more likely to report improved cough. Still, the investigators concluded that the overall picture did not suggest major differences in PROs by PD-L1 expression level, noting that global quality of life did not differ, and symptom improvement rates and time-to-deterioration measures generally aligned with the intent-to-treat population, judging by overlapping 95% confidence intervals and hazard ratios.
“These data support the PACIFIC regimen for the standard of care for stage III unresectable non–small cell lung cancer patients,” Dr. Garassino concluded.
Invited discussant Fabrice Barlesi, MD, PhD, of Aix-Marseille University, said that studies such as this one are important to ensure that investigator-implemented measures of response are calibrated to patient experiences. As an example, Dr. Barlesi noted that many clinicians would say that grade 2 diarrhea is a completely manageable adverse event, but not all patients would agree.
In this light, Dr. Barlesi said that the present findings are valuable, but they are not without flaws. He noted that 11 out of 13 symptoms from the quality of life lung cancer module were not reported, and that one-third of patients in the PACIFIC trial lacked PD-L1 expression level data.
Considering these shortcomings, and more broadly, difficulties comparing patient-reported outcome studies because of various measurement techniques, Dr. Barlesi called for standardization.
“We need to standardize the analysis of quality of life data,” Dr. Barlesi said. “We should correct for the multiplicity of tests. … we should identify some specific quality of life outcomes that we want to look at in the protocol.” He continued to suggest a variety of ideal characteristics for studies evaluating patient-reported outcomes, including defined statistical measures and protocols for missing data.
Without a standardized approach, “cross trial comparison will be a nightmare for all of us,” Dr. Barlesi said.
The study was funded by AstraZeneca. The investigators reported financial relationships with Roche, BMS, Lilly, and others.
SOURCE: Garassino et al. ELCC 2019. Abstract LBA2.
GENEVA – Level of programmed death-ligand 1 (PD-L1) expression does not impact patient-reported outcomes (PROs) among those receiving durvalumab for stage III non–small cell lung cancer (NSCLC), according to a retrospective analysis of the phase III PACIFIC trial.
The findings support durvalumab for all comers regardless of PD-L1 expression, reported lead author Marina Garassino, MD, of Fondazione IRCCS – Instituto Nazionale dei Tumori in Milan, who presented findings at the European Lung Cancer Congress.
The PACIFIC trial involved 713 patients with stage III NSCLC who did not progress after platinum-based concurrent chemoradiotherapy, demonstrating both improved progression-free and overall survival. Patients were randomized 2:1 to receive either durvalumab (10 mg/kg) or placebo IV every 2 weeks for up to 1 year. Out of 713 patients involved in the trial, 63% had PD-L1 tumor expression level data available for the present analysis, allowing for subgrouping into five categories: expression level of at least 25%, less than 25%, at least 1%, less than 1%, or unknown. The investigators compared PROs from these cohorts using the European Organisation for Research and Treatment of Cancer core quality of life questionnaire and lung cancer module (EORTC QLQ-C30 and -LC13). With scores ranging from 1 to 100 points, clinically meaningful differences were defined by score changes exceeding 10 points. Changes during treatment, from baseline to week 48, were analyzed by a mixed model for repeated measures, overall responses for improvement rates by logistic regression, and hazard ratios for time to deterioration (TTD) by a stratified Cox proportional-hazards model.
The investigators found that most PROs remained consistent over time, without clinically meaningful variations between PD-L1 expression levels. However, as with the entire PACIFIC treatment population, patients in the present analysis showed changes in some PROs. At the meeting presented by the European Society for Medical Oncology, Dr. Garassino noted that it would be unrealistic to describe all PRO comparisons; instead, she presented several examples. For one, in patients receiving durvalumab, dysphagia and alopecia improved in four out of five PD-L1 subgroups and all subgroups, respectively, while patients in the placebo arm reported improvements in both measures regardless of PD-L1 expression. Other improvements tended to favor the durvalumab group; for instance, compared with other subgroups, patients with PD-L1 expression of at least 25% were more likely to report improved chest pain, physical functioning, pain, emotional functioning, and hemoptysis. In contrast, patients receiving placebo with PD-L1 expression less than 25% were more likely to report improved cough. Still, the investigators concluded that the overall picture did not suggest major differences in PROs by PD-L1 expression level, noting that global quality of life did not differ, and symptom improvement rates and time-to-deterioration measures generally aligned with the intent-to-treat population, judging by overlapping 95% confidence intervals and hazard ratios.
“These data support the PACIFIC regimen for the standard of care for stage III unresectable non–small cell lung cancer patients,” Dr. Garassino concluded.
Invited discussant Fabrice Barlesi, MD, PhD, of Aix-Marseille University, said that studies such as this one are important to ensure that investigator-implemented measures of response are calibrated to patient experiences. As an example, Dr. Barlesi noted that many clinicians would say that grade 2 diarrhea is a completely manageable adverse event, but not all patients would agree.
In this light, Dr. Barlesi said that the present findings are valuable, but they are not without flaws. He noted that 11 out of 13 symptoms from the quality of life lung cancer module were not reported, and that one-third of patients in the PACIFIC trial lacked PD-L1 expression level data.
Considering these shortcomings, and more broadly, difficulties comparing patient-reported outcome studies because of various measurement techniques, Dr. Barlesi called for standardization.
“We need to standardize the analysis of quality of life data,” Dr. Barlesi said. “We should correct for the multiplicity of tests. … we should identify some specific quality of life outcomes that we want to look at in the protocol.” He continued to suggest a variety of ideal characteristics for studies evaluating patient-reported outcomes, including defined statistical measures and protocols for missing data.
Without a standardized approach, “cross trial comparison will be a nightmare for all of us,” Dr. Barlesi said.
The study was funded by AstraZeneca. The investigators reported financial relationships with Roche, BMS, Lilly, and others.
SOURCE: Garassino et al. ELCC 2019. Abstract LBA2.
GENEVA – Level of programmed death-ligand 1 (PD-L1) expression does not impact patient-reported outcomes (PROs) among those receiving durvalumab for stage III non–small cell lung cancer (NSCLC), according to a retrospective analysis of the phase III PACIFIC trial.
The findings support durvalumab for all comers regardless of PD-L1 expression, reported lead author Marina Garassino, MD, of Fondazione IRCCS – Instituto Nazionale dei Tumori in Milan, who presented findings at the European Lung Cancer Congress.
The PACIFIC trial involved 713 patients with stage III NSCLC who did not progress after platinum-based concurrent chemoradiotherapy, demonstrating both improved progression-free and overall survival. Patients were randomized 2:1 to receive either durvalumab (10 mg/kg) or placebo IV every 2 weeks for up to 1 year. Out of 713 patients involved in the trial, 63% had PD-L1 tumor expression level data available for the present analysis, allowing for subgrouping into five categories: expression level of at least 25%, less than 25%, at least 1%, less than 1%, or unknown. The investigators compared PROs from these cohorts using the European Organisation for Research and Treatment of Cancer core quality of life questionnaire and lung cancer module (EORTC QLQ-C30 and -LC13). With scores ranging from 1 to 100 points, clinically meaningful differences were defined by score changes exceeding 10 points. Changes during treatment, from baseline to week 48, were analyzed by a mixed model for repeated measures, overall responses for improvement rates by logistic regression, and hazard ratios for time to deterioration (TTD) by a stratified Cox proportional-hazards model.
The investigators found that most PROs remained consistent over time, without clinically meaningful variations between PD-L1 expression levels. However, as with the entire PACIFIC treatment population, patients in the present analysis showed changes in some PROs. At the meeting presented by the European Society for Medical Oncology, Dr. Garassino noted that it would be unrealistic to describe all PRO comparisons; instead, she presented several examples. For one, in patients receiving durvalumab, dysphagia and alopecia improved in four out of five PD-L1 subgroups and all subgroups, respectively, while patients in the placebo arm reported improvements in both measures regardless of PD-L1 expression. Other improvements tended to favor the durvalumab group; for instance, compared with other subgroups, patients with PD-L1 expression of at least 25% were more likely to report improved chest pain, physical functioning, pain, emotional functioning, and hemoptysis. In contrast, patients receiving placebo with PD-L1 expression less than 25% were more likely to report improved cough. Still, the investigators concluded that the overall picture did not suggest major differences in PROs by PD-L1 expression level, noting that global quality of life did not differ, and symptom improvement rates and time-to-deterioration measures generally aligned with the intent-to-treat population, judging by overlapping 95% confidence intervals and hazard ratios.
“These data support the PACIFIC regimen for the standard of care for stage III unresectable non–small cell lung cancer patients,” Dr. Garassino concluded.
Invited discussant Fabrice Barlesi, MD, PhD, of Aix-Marseille University, said that studies such as this one are important to ensure that investigator-implemented measures of response are calibrated to patient experiences. As an example, Dr. Barlesi noted that many clinicians would say that grade 2 diarrhea is a completely manageable adverse event, but not all patients would agree.
In this light, Dr. Barlesi said that the present findings are valuable, but they are not without flaws. He noted that 11 out of 13 symptoms from the quality of life lung cancer module were not reported, and that one-third of patients in the PACIFIC trial lacked PD-L1 expression level data.
Considering these shortcomings, and more broadly, difficulties comparing patient-reported outcome studies because of various measurement techniques, Dr. Barlesi called for standardization.
“We need to standardize the analysis of quality of life data,” Dr. Barlesi said. “We should correct for the multiplicity of tests. … we should identify some specific quality of life outcomes that we want to look at in the protocol.” He continued to suggest a variety of ideal characteristics for studies evaluating patient-reported outcomes, including defined statistical measures and protocols for missing data.
Without a standardized approach, “cross trial comparison will be a nightmare for all of us,” Dr. Barlesi said.
The study was funded by AstraZeneca. The investigators reported financial relationships with Roche, BMS, Lilly, and others.
SOURCE: Garassino et al. ELCC 2019. Abstract LBA2.
REPORTING FROM ELCC 2019
Treatment of Gout
Extended half-life clotting factors cut infusions, hike prices
More than a fifth of patients with hemophilia may now be using extended half-life (EHL) clotting factors, although the economic impact of these new treatments remains unclear.
Use of EHL factor VIII (FVIII) and IX (FIX) products surged from 10% of patients to 22% over an 18-month period ending in late 2017, Dr. Stacy E. Croteau and her colleagues reported in Haemophilia.
The increase appears to be mostly driven by prescribed prophylaxis rather than on-demand use of the products, wrote Dr. Croteau of Boston Children’s Hospital, and her coauthors. EHL dosages were similar to standard half-life (SHL) dosages and extended the time between infusions. But in the end, the higher cost of the EHL products actually drove up the price of prophylaxis, with a year of EHL FIX topping $1 million.
“Careful assessment of factor consumption and patient outcomes is needed to ensure general cost neutrality of this expensive therapy,” the researchers wrote. “Unless demonstrably offset by reduction in bleed doses, the net effect could be further increases in annual cost of care for this patient population.”
The study examined the use of SHL and EHL clotting factors in 7,893 adults and children with hemophilia A or B, who were being followed in the American Thrombosis and Hemostasis Network (ATHN) database. The authors sought to characterize changes in usage patterns for SHL and EHL factors, and to identify demographic and economic influences on them.
During the study, the number of patients using EHL products for both on-demand and prophylactic factor replacement increased. EHL FVIII use rose from 9% to 21%, and EHL FIX from 14% to 21%, especially among those with hemophilia B.
There were 6,437 patients with full data at both initial and final sampling. Among these, there was a 9.6% increase in the use of an EHL clotting factor by the end of the study (P less than .001). Patients with hemophilia A were less likely than hemophilia B patients to use an EHL product for prophylaxis.
While the EHL products did reduce the number of prophylactic infusions, they also cost much more, the investigators found.
The standard dose of SHL FVIII is 40 IU/g infused three times a week. The projected cost of 156 annual infusions is $690,144. EHL FVII, dosed at 50 IU/kg, cuts infusions to twice a week. The annual projected cost of the 104 infusions is $753,480.
The standard dose of SHL FIX is 67 IU/kg, infused twice a week. The annual projected cost of 104 infusions is $697,497. EHL FIX, dosed at 75 IU/Kg, halves the number of infusions. But the price for those 52 treatments exceeds $1 million ($1,015,560). Despite the cost, however, just 43 patients switched from an EHL product to a SHL factor product during the study period.
Insurance type appeared to have little influence on the choice of SHL or EHL clotting factors. Across payer types, a similar proportion of patients started using them, and 71% were covered by private insurance or Medicaid.
The study was funded HTRS/ATHN Dataset Research Engagement and a DREAM Award from the Hemostasis and Thrombosis Research Society. Dr. Croteau reported consulting for Bayer, Bioverativ, Biomarin, CSL-Behring, and other companies.
SOURCE: Croteau SE et al. Haemophilia. 2019 Apr 17. doi: 10.1111/hae.13758.
More than a fifth of patients with hemophilia may now be using extended half-life (EHL) clotting factors, although the economic impact of these new treatments remains unclear.
Use of EHL factor VIII (FVIII) and IX (FIX) products surged from 10% of patients to 22% over an 18-month period ending in late 2017, Dr. Stacy E. Croteau and her colleagues reported in Haemophilia.
The increase appears to be mostly driven by prescribed prophylaxis rather than on-demand use of the products, wrote Dr. Croteau of Boston Children’s Hospital, and her coauthors. EHL dosages were similar to standard half-life (SHL) dosages and extended the time between infusions. But in the end, the higher cost of the EHL products actually drove up the price of prophylaxis, with a year of EHL FIX topping $1 million.
“Careful assessment of factor consumption and patient outcomes is needed to ensure general cost neutrality of this expensive therapy,” the researchers wrote. “Unless demonstrably offset by reduction in bleed doses, the net effect could be further increases in annual cost of care for this patient population.”
The study examined the use of SHL and EHL clotting factors in 7,893 adults and children with hemophilia A or B, who were being followed in the American Thrombosis and Hemostasis Network (ATHN) database. The authors sought to characterize changes in usage patterns for SHL and EHL factors, and to identify demographic and economic influences on them.
During the study, the number of patients using EHL products for both on-demand and prophylactic factor replacement increased. EHL FVIII use rose from 9% to 21%, and EHL FIX from 14% to 21%, especially among those with hemophilia B.
There were 6,437 patients with full data at both initial and final sampling. Among these, there was a 9.6% increase in the use of an EHL clotting factor by the end of the study (P less than .001). Patients with hemophilia A were less likely than hemophilia B patients to use an EHL product for prophylaxis.
While the EHL products did reduce the number of prophylactic infusions, they also cost much more, the investigators found.
The standard dose of SHL FVIII is 40 IU/g infused three times a week. The projected cost of 156 annual infusions is $690,144. EHL FVII, dosed at 50 IU/kg, cuts infusions to twice a week. The annual projected cost of the 104 infusions is $753,480.
The standard dose of SHL FIX is 67 IU/kg, infused twice a week. The annual projected cost of 104 infusions is $697,497. EHL FIX, dosed at 75 IU/Kg, halves the number of infusions. But the price for those 52 treatments exceeds $1 million ($1,015,560). Despite the cost, however, just 43 patients switched from an EHL product to a SHL factor product during the study period.
Insurance type appeared to have little influence on the choice of SHL or EHL clotting factors. Across payer types, a similar proportion of patients started using them, and 71% were covered by private insurance or Medicaid.
The study was funded HTRS/ATHN Dataset Research Engagement and a DREAM Award from the Hemostasis and Thrombosis Research Society. Dr. Croteau reported consulting for Bayer, Bioverativ, Biomarin, CSL-Behring, and other companies.
SOURCE: Croteau SE et al. Haemophilia. 2019 Apr 17. doi: 10.1111/hae.13758.
More than a fifth of patients with hemophilia may now be using extended half-life (EHL) clotting factors, although the economic impact of these new treatments remains unclear.
Use of EHL factor VIII (FVIII) and IX (FIX) products surged from 10% of patients to 22% over an 18-month period ending in late 2017, Dr. Stacy E. Croteau and her colleagues reported in Haemophilia.
The increase appears to be mostly driven by prescribed prophylaxis rather than on-demand use of the products, wrote Dr. Croteau of Boston Children’s Hospital, and her coauthors. EHL dosages were similar to standard half-life (SHL) dosages and extended the time between infusions. But in the end, the higher cost of the EHL products actually drove up the price of prophylaxis, with a year of EHL FIX topping $1 million.
“Careful assessment of factor consumption and patient outcomes is needed to ensure general cost neutrality of this expensive therapy,” the researchers wrote. “Unless demonstrably offset by reduction in bleed doses, the net effect could be further increases in annual cost of care for this patient population.”
The study examined the use of SHL and EHL clotting factors in 7,893 adults and children with hemophilia A or B, who were being followed in the American Thrombosis and Hemostasis Network (ATHN) database. The authors sought to characterize changes in usage patterns for SHL and EHL factors, and to identify demographic and economic influences on them.
During the study, the number of patients using EHL products for both on-demand and prophylactic factor replacement increased. EHL FVIII use rose from 9% to 21%, and EHL FIX from 14% to 21%, especially among those with hemophilia B.
There were 6,437 patients with full data at both initial and final sampling. Among these, there was a 9.6% increase in the use of an EHL clotting factor by the end of the study (P less than .001). Patients with hemophilia A were less likely than hemophilia B patients to use an EHL product for prophylaxis.
While the EHL products did reduce the number of prophylactic infusions, they also cost much more, the investigators found.
The standard dose of SHL FVIII is 40 IU/g infused three times a week. The projected cost of 156 annual infusions is $690,144. EHL FVII, dosed at 50 IU/kg, cuts infusions to twice a week. The annual projected cost of the 104 infusions is $753,480.
The standard dose of SHL FIX is 67 IU/kg, infused twice a week. The annual projected cost of 104 infusions is $697,497. EHL FIX, dosed at 75 IU/Kg, halves the number of infusions. But the price for those 52 treatments exceeds $1 million ($1,015,560). Despite the cost, however, just 43 patients switched from an EHL product to a SHL factor product during the study period.
Insurance type appeared to have little influence on the choice of SHL or EHL clotting factors. Across payer types, a similar proportion of patients started using them, and 71% were covered by private insurance or Medicaid.
The study was funded HTRS/ATHN Dataset Research Engagement and a DREAM Award from the Hemostasis and Thrombosis Research Society. Dr. Croteau reported consulting for Bayer, Bioverativ, Biomarin, CSL-Behring, and other companies.
SOURCE: Croteau SE et al. Haemophilia. 2019 Apr 17. doi: 10.1111/hae.13758.
FROM HAEMOPHILIA