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American College of Rheumatology (ACR): Annual Scientific Meeting
MACRA’s near and potential long-term future outlined for rheumatology
WASHINGTON – Now that implementation of the Medicare Access and CHIP Reauthorization Act is on rheumatologists’ doorsteps, figuring out what is required in 2017 is imperative to avoid future penalties and maximize the chance of earning a bonus.
Recent announcements from the Centers for Medicare & Medicaid Services (CMS) on performance thresholds and how to meet them in 2017 give rheumatologists a great shot at not getting penalized when payment adjustments begin in 2019.
However, efforts by the ACR to create new rheumatology-focused APMs could play a major role in changing that, said Dr. Harvey, clinical director of the Arthritis Treatment Center at Tufts Medical Center, Boston, and former chair of the ACR’s Committee on Government Affairs.
The MIPS option in MACRA is “a repackaging” of old programs, including Meaningful Use (which is now called Advancing Care Information), value-based modifiers, and the Physician Quality Reporting System (PQRS). “One silver lining to this massive piece of legislation is that it’s actually less downside risk than if you had continued with Meaningful Use, PQRS, and value-based modifier,” Dr. Harvey said.
MIPS is onerous by design, in Dr. Harvey’s opinion. “CMS does not want to continue the fee-for-service arrangement and MIPS is basically fee-for-service with a bit of pay-for-performance bolted on top of it. They’ve already stated that they want to push every provider into alternative payment model–type reimbursements going forward.”
Rheumatologists aren’t eligible for MIPS if they see fewer than 100 Medicare patients per year or if they bill less than $30,000 in Medicare fees. For MIPS-eligible physicians, adjustments to Medicare payments begin in 2019 based on 2017 quality reporting data. Physicians will still receive yearly 0.5% increases in Medicare pay in 2017-2019 and 0% each year through 2025 before any adjustments are made based on the MIPS score. Participation in the MIPS pathway gives the potential for payment adjustments starting at plus or minus 4% in 2019, plus or minus 5% in 2020, plus or minus 7% in 2021, and plus or minus 9% in 2022 and beyond, based on how rheumatologists compare against their peers.
Targets for 2017 and adjustments beyond 2017
Each year in November, CMS will announce the base performance threshold goal that physicians will need to reach in the following year in order to avoid negative Medicare payment adjustments 2 years later.
Each year’s threshold will be based on the data collected from the prior year. For the year starting Jan. 1, 2017, in order to avoid a 4% cut in their Medicare Part B base rate payment in 2019, rheumatologists will need to meet a base performance threshold score of just 3 out of 100.
“Basically, if you participate in a program in any way whatsoever, you can hit this target,” Dr. Harvey said.
In 2017, getting a score of 70 or more out of 100 puts rheumatologists into a high performance category that makes them eligible for a piece of the $500 million pool of positive payment adjustments that will be available in each of the first 6 years of MIPS.
Providers who score less than 3 out of 100 will get the maximum penalty – a 4% cut in their 2019 Medicare payment rate. Further, in 2017, only 90 days of reporting is required to qualify for positive adjustments in 2019.
The base performance threshold will certainly go up for 2018 to “probably 30, 40, 50; something like that,” Dr. Harvey said.
Knowing the threshold in advance should help rheumatologists to predict by the middle of each year whether they are going to make it, but how much of any increase (or decrease) in payment adjustment they will have 2 years hence will be very difficult to know, he said, because each year the adjustment must be budget neutral and is dependent on how many physicians are above and below the threshold.
The MIPS score is based on four categories that total up to 100 points:
Quality (60% of 2017 score)
The quality category is determined by six measures that are worth 10 points each. All of the quality domains from PQRS are gone, and out of those six measures providers must have one cross-cutting measure and one outcome measure, or just one high-priority measure. Since rheumatology does not yet have any designated outcome measures, rheumatologists will need to report other designated measures. For each of these six required measures, a provider would earn 3 points for reaching the benchmark, and then the score could be increased to 4-10 points per measure based on a decile system that determines the provider’s performance against others who have met the benchmark for that measure.
Of the 13 quality metrics that are in the rheumatology quality measure set, 7 are not specific to rheumatology (advanced directive documentation, body mass index screening and follow-up, taking a comprehensive medication list, tobacco screening in adolescents, tobacco screening in adults, hypertension screening and follow-up, and sending consult note to referring doctor), whereas 6 are (TB screening within 6 months of starting a biologic, yearly TB screening on biologics, measuring rheumatoid arthritis [RA] disease activity, measuring RA functional assessment, documenting RA prognosis, and RA steroid management).
The quality category will account for 50% of the MIPS score in 2018.
Resource use (0% of 2017 score)
“The fact that the resource use part of the equation has been set to 0% for the 2017 performance year is a really good thing for rheumatologists because we use some of the most expensive drugs around,” Dr. Harvey said. “Part of the reason that CMS did this is that they are having trouble accounting for the fact that they have easy access to Part B cost data – infusion cost data – but they don’t have very good access to Part D self-injectable drug cost data.”
“We are going to make it a key advocacy point that they appropriately take into account cost in future years,” he added.
While the resource use category of MIPS contributes nothing to the 2017 MIPS score, it will increase to 10% in 2018 and by 2021 it’s anticipated to be 30% of the MIPS score, while the quality category is anticipated to drop to 30%.
Clinical practice improvement activities (15% of 2017 score)
This part includes more than 90 proposed activities to count toward the category’s score, including patient engagement activities, care coordination, extended office hours, and participation in a qualified clinical data registry (QCDR), such as the ACR’s RISE Registry, which is already a certified QCDR. A total of 40 points in this category gives full credit for the 15 percentage point value given to it for 2017.
All of the proposed activities for 2017 are weighted as medium (10 points) or high weight (20 points). For example, 40 points could be earned by meeting two medium-weight measures and one high-weight measure.
The clinical practice improvement activities category will stay at 15% of the MIPS score in 2018.
Advancing care information (25% of 2017 score)
“This is another one that gets complicated, but there’s one key take-home message: This is way easier than Meaningful Use has ever been,” Dr. Harvey said. There are 100 points needed in the advancing care information category in order to get the full 25 percentage points that it accounts for in the 2017 MIPS score.
For reporting on five required measures (electronic health record [EHR] security analysis, e-prescribing, patient access to an EHR, and being able to send and accept summary of care documents), a provider will earn 50 points.
Another 90 performance points are available for reporting certain information, and this is based on a decile system just like the quality category in which a rheumatologist’s performance is measured against other rheumatologists who have met the benchmark for each particular measure. These optional measures include providing patient-specific educational information; patients being able to view, download, and transmit their own medical records; secure messaging; acceptance of patient-generated health data; medication reconciliation; and submitting data to a state immunization registry.
Another 15 bonus points are available for additional public health reporting and reporting to CMS using a certified EHR or QCDR.
All these measures together give providers the potential to earn 155 points toward the 100-point threshold.
“If you’re already doing Meaningful Use, chances are you’re going to do really well in this area,” he said.
The advancing care information category will stay at 25% of the MIPS score in 2018.
Problems with current APMs
Under MACRA, participation in an APM means that the physician is exempt from MIPS and will receive a 5% lump sum bonus per year in 2019-2024, a higher annual increase in fee-for-service revenues, and the general benefits of participating in an APM. However, few rheumatologists will qualify for the APM pathway, and there are no rheumatology-specific APMs in existence.
Most current APMs are “shared savings” programs where if the physician or health system can reduce spending below the expected levels, then the provider receives a share of the payer’s savings. However, these shared-savings APMs all still use a fee-for-service structure, which makes them just a different form of pay for performance, according to Mr. Miller.
Physicians still don’t get paid for unfunded or underfunded services, and physicians who are already efficient receive little or no additional revenue and may be forced out of business, while physicians who have been practicing inefficiently or inappropriately are paid more than conservative physicians. There’s also the potential for rewarding the denial of needed care. Physicians in shared-savings APMs are also placed at risk for costs they cannot control and for random variations in spending. And most of all, the shared savings bonuses are temporary and when there are no more savings to be generated, physicians are underpaid, Mr. Miller said.
During 2013-2015, 46%-48% of Medicare shared-savings accountable care organizations (ACOs) increased their Medicare spending rather than reduced it, and only 24%-30% of the ACOs received shared-savings payments. In each year, Medicare spent more than it saved, with net losses ranging from $50 million to $216 million. This happened because physicians in the programs still got paid with fee-for-service payments, Mr. Miller said.
Creating rheumatology-focused APMs
MACRA designated the development of the Physician-Focused Payment Model Technical Advisory Committee, of which Mr. Miller is a member, to solicit and review physician-focused payment models and make recommendations to CMS about which ones to implement.
Physician-focused payment models got their start through pioneering work by physicians who obtained data from insurers to find ways to reach out proactively to patients to address problems before patients are hospitalized. Through these efforts, they have reduced cost and increased patient satisfaction while also increasing payment to physicians by supporting “medical home” services, according to Dr. Miller.
These efforts to create APMs that support high-quality, physician-directed care begin by identifying avoidable spending that varies from specialty to specialty and from condition to condition. Then they address barriers in the current fee-for-service system – such as no payment for many high-value services and insufficient revenue to cover costs when using fewer or low-cost services – by providing flexible, adequate payment while requiring physicians to take responsibility for the things they said could be avoidable when paid in that way. However, this responsibility must be focused on what a particular physician can influence, Mr. Miller noted.
Rheumatologists could be helped by these physician-focused payment models because they receive less than 10% of the total Medicare health care spending per patient whose care was directed by a rheumatologist. In that case, finding ways to drop total spending per patient by 5% could at the same time give rheumatologists a 25% increase in payment while also saving Medicare 3% overall, he said.
Rheumatologists are best set up to take condition-based payments that are geared to keep patients out of the hospital, rather than the hospital episode–based payments that have dominated APMs in existence so far. Central to this condition-based model is getting the right diagnosis at the start, so payment for getting the correct diagnosis would be critical.
APMs designed for rheumatologists could take into account the diseases often seen by a rheumatologist, such as RA, and then identify opportunities to improve care and reduce costs while identifying barriers in the current payment system for achieving those goals, Mr. Miller said. These opportunities and barriers would vary from condition to condition. In some cases, particularly for low-frequency conditions, there may not need to be a new payment model established and it could be done through fee-for-service.
Ideally, these condition-based payment models for specialists such as rheumatologists would exist within the “medical neighborhood” of primary care physicians who could refer to them when necessary. Specialists would be accountable for the aspects of care that they can control, such as avoiding unnecessary tests and procedures and avoiding infections and complications.
“That’s building the ACO from the bottom up, rather than what Medicare is trying to do, which is to create it from the top down,” Mr. Miller said.
Mr. Miller noted that it will be important for specialties such as rheumatology to define the cost data it needs in order to develop condition-based payment models.
Dr. Harvey had no relevant disclosures. Mr. Miller has no financial relationships with any commercial interests.
WASHINGTON – Now that implementation of the Medicare Access and CHIP Reauthorization Act is on rheumatologists’ doorsteps, figuring out what is required in 2017 is imperative to avoid future penalties and maximize the chance of earning a bonus.
Recent announcements from the Centers for Medicare & Medicaid Services (CMS) on performance thresholds and how to meet them in 2017 give rheumatologists a great shot at not getting penalized when payment adjustments begin in 2019.
However, efforts by the ACR to create new rheumatology-focused APMs could play a major role in changing that, said Dr. Harvey, clinical director of the Arthritis Treatment Center at Tufts Medical Center, Boston, and former chair of the ACR’s Committee on Government Affairs.
The MIPS option in MACRA is “a repackaging” of old programs, including Meaningful Use (which is now called Advancing Care Information), value-based modifiers, and the Physician Quality Reporting System (PQRS). “One silver lining to this massive piece of legislation is that it’s actually less downside risk than if you had continued with Meaningful Use, PQRS, and value-based modifier,” Dr. Harvey said.
MIPS is onerous by design, in Dr. Harvey’s opinion. “CMS does not want to continue the fee-for-service arrangement and MIPS is basically fee-for-service with a bit of pay-for-performance bolted on top of it. They’ve already stated that they want to push every provider into alternative payment model–type reimbursements going forward.”
Rheumatologists aren’t eligible for MIPS if they see fewer than 100 Medicare patients per year or if they bill less than $30,000 in Medicare fees. For MIPS-eligible physicians, adjustments to Medicare payments begin in 2019 based on 2017 quality reporting data. Physicians will still receive yearly 0.5% increases in Medicare pay in 2017-2019 and 0% each year through 2025 before any adjustments are made based on the MIPS score. Participation in the MIPS pathway gives the potential for payment adjustments starting at plus or minus 4% in 2019, plus or minus 5% in 2020, plus or minus 7% in 2021, and plus or minus 9% in 2022 and beyond, based on how rheumatologists compare against their peers.
Targets for 2017 and adjustments beyond 2017
Each year in November, CMS will announce the base performance threshold goal that physicians will need to reach in the following year in order to avoid negative Medicare payment adjustments 2 years later.
Each year’s threshold will be based on the data collected from the prior year. For the year starting Jan. 1, 2017, in order to avoid a 4% cut in their Medicare Part B base rate payment in 2019, rheumatologists will need to meet a base performance threshold score of just 3 out of 100.
“Basically, if you participate in a program in any way whatsoever, you can hit this target,” Dr. Harvey said.
In 2017, getting a score of 70 or more out of 100 puts rheumatologists into a high performance category that makes them eligible for a piece of the $500 million pool of positive payment adjustments that will be available in each of the first 6 years of MIPS.
Providers who score less than 3 out of 100 will get the maximum penalty – a 4% cut in their 2019 Medicare payment rate. Further, in 2017, only 90 days of reporting is required to qualify for positive adjustments in 2019.
The base performance threshold will certainly go up for 2018 to “probably 30, 40, 50; something like that,” Dr. Harvey said.
Knowing the threshold in advance should help rheumatologists to predict by the middle of each year whether they are going to make it, but how much of any increase (or decrease) in payment adjustment they will have 2 years hence will be very difficult to know, he said, because each year the adjustment must be budget neutral and is dependent on how many physicians are above and below the threshold.
The MIPS score is based on four categories that total up to 100 points:
Quality (60% of 2017 score)
The quality category is determined by six measures that are worth 10 points each. All of the quality domains from PQRS are gone, and out of those six measures providers must have one cross-cutting measure and one outcome measure, or just one high-priority measure. Since rheumatology does not yet have any designated outcome measures, rheumatologists will need to report other designated measures. For each of these six required measures, a provider would earn 3 points for reaching the benchmark, and then the score could be increased to 4-10 points per measure based on a decile system that determines the provider’s performance against others who have met the benchmark for that measure.
Of the 13 quality metrics that are in the rheumatology quality measure set, 7 are not specific to rheumatology (advanced directive documentation, body mass index screening and follow-up, taking a comprehensive medication list, tobacco screening in adolescents, tobacco screening in adults, hypertension screening and follow-up, and sending consult note to referring doctor), whereas 6 are (TB screening within 6 months of starting a biologic, yearly TB screening on biologics, measuring rheumatoid arthritis [RA] disease activity, measuring RA functional assessment, documenting RA prognosis, and RA steroid management).
The quality category will account for 50% of the MIPS score in 2018.
Resource use (0% of 2017 score)
“The fact that the resource use part of the equation has been set to 0% for the 2017 performance year is a really good thing for rheumatologists because we use some of the most expensive drugs around,” Dr. Harvey said. “Part of the reason that CMS did this is that they are having trouble accounting for the fact that they have easy access to Part B cost data – infusion cost data – but they don’t have very good access to Part D self-injectable drug cost data.”
“We are going to make it a key advocacy point that they appropriately take into account cost in future years,” he added.
While the resource use category of MIPS contributes nothing to the 2017 MIPS score, it will increase to 10% in 2018 and by 2021 it’s anticipated to be 30% of the MIPS score, while the quality category is anticipated to drop to 30%.
Clinical practice improvement activities (15% of 2017 score)
This part includes more than 90 proposed activities to count toward the category’s score, including patient engagement activities, care coordination, extended office hours, and participation in a qualified clinical data registry (QCDR), such as the ACR’s RISE Registry, which is already a certified QCDR. A total of 40 points in this category gives full credit for the 15 percentage point value given to it for 2017.
All of the proposed activities for 2017 are weighted as medium (10 points) or high weight (20 points). For example, 40 points could be earned by meeting two medium-weight measures and one high-weight measure.
The clinical practice improvement activities category will stay at 15% of the MIPS score in 2018.
Advancing care information (25% of 2017 score)
“This is another one that gets complicated, but there’s one key take-home message: This is way easier than Meaningful Use has ever been,” Dr. Harvey said. There are 100 points needed in the advancing care information category in order to get the full 25 percentage points that it accounts for in the 2017 MIPS score.
For reporting on five required measures (electronic health record [EHR] security analysis, e-prescribing, patient access to an EHR, and being able to send and accept summary of care documents), a provider will earn 50 points.
Another 90 performance points are available for reporting certain information, and this is based on a decile system just like the quality category in which a rheumatologist’s performance is measured against other rheumatologists who have met the benchmark for each particular measure. These optional measures include providing patient-specific educational information; patients being able to view, download, and transmit their own medical records; secure messaging; acceptance of patient-generated health data; medication reconciliation; and submitting data to a state immunization registry.
Another 15 bonus points are available for additional public health reporting and reporting to CMS using a certified EHR or QCDR.
All these measures together give providers the potential to earn 155 points toward the 100-point threshold.
“If you’re already doing Meaningful Use, chances are you’re going to do really well in this area,” he said.
The advancing care information category will stay at 25% of the MIPS score in 2018.
Problems with current APMs
Under MACRA, participation in an APM means that the physician is exempt from MIPS and will receive a 5% lump sum bonus per year in 2019-2024, a higher annual increase in fee-for-service revenues, and the general benefits of participating in an APM. However, few rheumatologists will qualify for the APM pathway, and there are no rheumatology-specific APMs in existence.
Most current APMs are “shared savings” programs where if the physician or health system can reduce spending below the expected levels, then the provider receives a share of the payer’s savings. However, these shared-savings APMs all still use a fee-for-service structure, which makes them just a different form of pay for performance, according to Mr. Miller.
Physicians still don’t get paid for unfunded or underfunded services, and physicians who are already efficient receive little or no additional revenue and may be forced out of business, while physicians who have been practicing inefficiently or inappropriately are paid more than conservative physicians. There’s also the potential for rewarding the denial of needed care. Physicians in shared-savings APMs are also placed at risk for costs they cannot control and for random variations in spending. And most of all, the shared savings bonuses are temporary and when there are no more savings to be generated, physicians are underpaid, Mr. Miller said.
During 2013-2015, 46%-48% of Medicare shared-savings accountable care organizations (ACOs) increased their Medicare spending rather than reduced it, and only 24%-30% of the ACOs received shared-savings payments. In each year, Medicare spent more than it saved, with net losses ranging from $50 million to $216 million. This happened because physicians in the programs still got paid with fee-for-service payments, Mr. Miller said.
Creating rheumatology-focused APMs
MACRA designated the development of the Physician-Focused Payment Model Technical Advisory Committee, of which Mr. Miller is a member, to solicit and review physician-focused payment models and make recommendations to CMS about which ones to implement.
Physician-focused payment models got their start through pioneering work by physicians who obtained data from insurers to find ways to reach out proactively to patients to address problems before patients are hospitalized. Through these efforts, they have reduced cost and increased patient satisfaction while also increasing payment to physicians by supporting “medical home” services, according to Dr. Miller.
These efforts to create APMs that support high-quality, physician-directed care begin by identifying avoidable spending that varies from specialty to specialty and from condition to condition. Then they address barriers in the current fee-for-service system – such as no payment for many high-value services and insufficient revenue to cover costs when using fewer or low-cost services – by providing flexible, adequate payment while requiring physicians to take responsibility for the things they said could be avoidable when paid in that way. However, this responsibility must be focused on what a particular physician can influence, Mr. Miller noted.
Rheumatologists could be helped by these physician-focused payment models because they receive less than 10% of the total Medicare health care spending per patient whose care was directed by a rheumatologist. In that case, finding ways to drop total spending per patient by 5% could at the same time give rheumatologists a 25% increase in payment while also saving Medicare 3% overall, he said.
Rheumatologists are best set up to take condition-based payments that are geared to keep patients out of the hospital, rather than the hospital episode–based payments that have dominated APMs in existence so far. Central to this condition-based model is getting the right diagnosis at the start, so payment for getting the correct diagnosis would be critical.
APMs designed for rheumatologists could take into account the diseases often seen by a rheumatologist, such as RA, and then identify opportunities to improve care and reduce costs while identifying barriers in the current payment system for achieving those goals, Mr. Miller said. These opportunities and barriers would vary from condition to condition. In some cases, particularly for low-frequency conditions, there may not need to be a new payment model established and it could be done through fee-for-service.
Ideally, these condition-based payment models for specialists such as rheumatologists would exist within the “medical neighborhood” of primary care physicians who could refer to them when necessary. Specialists would be accountable for the aspects of care that they can control, such as avoiding unnecessary tests and procedures and avoiding infections and complications.
“That’s building the ACO from the bottom up, rather than what Medicare is trying to do, which is to create it from the top down,” Mr. Miller said.
Mr. Miller noted that it will be important for specialties such as rheumatology to define the cost data it needs in order to develop condition-based payment models.
Dr. Harvey had no relevant disclosures. Mr. Miller has no financial relationships with any commercial interests.
WASHINGTON – Now that implementation of the Medicare Access and CHIP Reauthorization Act is on rheumatologists’ doorsteps, figuring out what is required in 2017 is imperative to avoid future penalties and maximize the chance of earning a bonus.
Recent announcements from the Centers for Medicare & Medicaid Services (CMS) on performance thresholds and how to meet them in 2017 give rheumatologists a great shot at not getting penalized when payment adjustments begin in 2019.
However, efforts by the ACR to create new rheumatology-focused APMs could play a major role in changing that, said Dr. Harvey, clinical director of the Arthritis Treatment Center at Tufts Medical Center, Boston, and former chair of the ACR’s Committee on Government Affairs.
The MIPS option in MACRA is “a repackaging” of old programs, including Meaningful Use (which is now called Advancing Care Information), value-based modifiers, and the Physician Quality Reporting System (PQRS). “One silver lining to this massive piece of legislation is that it’s actually less downside risk than if you had continued with Meaningful Use, PQRS, and value-based modifier,” Dr. Harvey said.
MIPS is onerous by design, in Dr. Harvey’s opinion. “CMS does not want to continue the fee-for-service arrangement and MIPS is basically fee-for-service with a bit of pay-for-performance bolted on top of it. They’ve already stated that they want to push every provider into alternative payment model–type reimbursements going forward.”
Rheumatologists aren’t eligible for MIPS if they see fewer than 100 Medicare patients per year or if they bill less than $30,000 in Medicare fees. For MIPS-eligible physicians, adjustments to Medicare payments begin in 2019 based on 2017 quality reporting data. Physicians will still receive yearly 0.5% increases in Medicare pay in 2017-2019 and 0% each year through 2025 before any adjustments are made based on the MIPS score. Participation in the MIPS pathway gives the potential for payment adjustments starting at plus or minus 4% in 2019, plus or minus 5% in 2020, plus or minus 7% in 2021, and plus or minus 9% in 2022 and beyond, based on how rheumatologists compare against their peers.
Targets for 2017 and adjustments beyond 2017
Each year in November, CMS will announce the base performance threshold goal that physicians will need to reach in the following year in order to avoid negative Medicare payment adjustments 2 years later.
Each year’s threshold will be based on the data collected from the prior year. For the year starting Jan. 1, 2017, in order to avoid a 4% cut in their Medicare Part B base rate payment in 2019, rheumatologists will need to meet a base performance threshold score of just 3 out of 100.
“Basically, if you participate in a program in any way whatsoever, you can hit this target,” Dr. Harvey said.
In 2017, getting a score of 70 or more out of 100 puts rheumatologists into a high performance category that makes them eligible for a piece of the $500 million pool of positive payment adjustments that will be available in each of the first 6 years of MIPS.
Providers who score less than 3 out of 100 will get the maximum penalty – a 4% cut in their 2019 Medicare payment rate. Further, in 2017, only 90 days of reporting is required to qualify for positive adjustments in 2019.
The base performance threshold will certainly go up for 2018 to “probably 30, 40, 50; something like that,” Dr. Harvey said.
Knowing the threshold in advance should help rheumatologists to predict by the middle of each year whether they are going to make it, but how much of any increase (or decrease) in payment adjustment they will have 2 years hence will be very difficult to know, he said, because each year the adjustment must be budget neutral and is dependent on how many physicians are above and below the threshold.
The MIPS score is based on four categories that total up to 100 points:
Quality (60% of 2017 score)
The quality category is determined by six measures that are worth 10 points each. All of the quality domains from PQRS are gone, and out of those six measures providers must have one cross-cutting measure and one outcome measure, or just one high-priority measure. Since rheumatology does not yet have any designated outcome measures, rheumatologists will need to report other designated measures. For each of these six required measures, a provider would earn 3 points for reaching the benchmark, and then the score could be increased to 4-10 points per measure based on a decile system that determines the provider’s performance against others who have met the benchmark for that measure.
Of the 13 quality metrics that are in the rheumatology quality measure set, 7 are not specific to rheumatology (advanced directive documentation, body mass index screening and follow-up, taking a comprehensive medication list, tobacco screening in adolescents, tobacco screening in adults, hypertension screening and follow-up, and sending consult note to referring doctor), whereas 6 are (TB screening within 6 months of starting a biologic, yearly TB screening on biologics, measuring rheumatoid arthritis [RA] disease activity, measuring RA functional assessment, documenting RA prognosis, and RA steroid management).
The quality category will account for 50% of the MIPS score in 2018.
Resource use (0% of 2017 score)
“The fact that the resource use part of the equation has been set to 0% for the 2017 performance year is a really good thing for rheumatologists because we use some of the most expensive drugs around,” Dr. Harvey said. “Part of the reason that CMS did this is that they are having trouble accounting for the fact that they have easy access to Part B cost data – infusion cost data – but they don’t have very good access to Part D self-injectable drug cost data.”
“We are going to make it a key advocacy point that they appropriately take into account cost in future years,” he added.
While the resource use category of MIPS contributes nothing to the 2017 MIPS score, it will increase to 10% in 2018 and by 2021 it’s anticipated to be 30% of the MIPS score, while the quality category is anticipated to drop to 30%.
Clinical practice improvement activities (15% of 2017 score)
This part includes more than 90 proposed activities to count toward the category’s score, including patient engagement activities, care coordination, extended office hours, and participation in a qualified clinical data registry (QCDR), such as the ACR’s RISE Registry, which is already a certified QCDR. A total of 40 points in this category gives full credit for the 15 percentage point value given to it for 2017.
All of the proposed activities for 2017 are weighted as medium (10 points) or high weight (20 points). For example, 40 points could be earned by meeting two medium-weight measures and one high-weight measure.
The clinical practice improvement activities category will stay at 15% of the MIPS score in 2018.
Advancing care information (25% of 2017 score)
“This is another one that gets complicated, but there’s one key take-home message: This is way easier than Meaningful Use has ever been,” Dr. Harvey said. There are 100 points needed in the advancing care information category in order to get the full 25 percentage points that it accounts for in the 2017 MIPS score.
For reporting on five required measures (electronic health record [EHR] security analysis, e-prescribing, patient access to an EHR, and being able to send and accept summary of care documents), a provider will earn 50 points.
Another 90 performance points are available for reporting certain information, and this is based on a decile system just like the quality category in which a rheumatologist’s performance is measured against other rheumatologists who have met the benchmark for each particular measure. These optional measures include providing patient-specific educational information; patients being able to view, download, and transmit their own medical records; secure messaging; acceptance of patient-generated health data; medication reconciliation; and submitting data to a state immunization registry.
Another 15 bonus points are available for additional public health reporting and reporting to CMS using a certified EHR or QCDR.
All these measures together give providers the potential to earn 155 points toward the 100-point threshold.
“If you’re already doing Meaningful Use, chances are you’re going to do really well in this area,” he said.
The advancing care information category will stay at 25% of the MIPS score in 2018.
Problems with current APMs
Under MACRA, participation in an APM means that the physician is exempt from MIPS and will receive a 5% lump sum bonus per year in 2019-2024, a higher annual increase in fee-for-service revenues, and the general benefits of participating in an APM. However, few rheumatologists will qualify for the APM pathway, and there are no rheumatology-specific APMs in existence.
Most current APMs are “shared savings” programs where if the physician or health system can reduce spending below the expected levels, then the provider receives a share of the payer’s savings. However, these shared-savings APMs all still use a fee-for-service structure, which makes them just a different form of pay for performance, according to Mr. Miller.
Physicians still don’t get paid for unfunded or underfunded services, and physicians who are already efficient receive little or no additional revenue and may be forced out of business, while physicians who have been practicing inefficiently or inappropriately are paid more than conservative physicians. There’s also the potential for rewarding the denial of needed care. Physicians in shared-savings APMs are also placed at risk for costs they cannot control and for random variations in spending. And most of all, the shared savings bonuses are temporary and when there are no more savings to be generated, physicians are underpaid, Mr. Miller said.
During 2013-2015, 46%-48% of Medicare shared-savings accountable care organizations (ACOs) increased their Medicare spending rather than reduced it, and only 24%-30% of the ACOs received shared-savings payments. In each year, Medicare spent more than it saved, with net losses ranging from $50 million to $216 million. This happened because physicians in the programs still got paid with fee-for-service payments, Mr. Miller said.
Creating rheumatology-focused APMs
MACRA designated the development of the Physician-Focused Payment Model Technical Advisory Committee, of which Mr. Miller is a member, to solicit and review physician-focused payment models and make recommendations to CMS about which ones to implement.
Physician-focused payment models got their start through pioneering work by physicians who obtained data from insurers to find ways to reach out proactively to patients to address problems before patients are hospitalized. Through these efforts, they have reduced cost and increased patient satisfaction while also increasing payment to physicians by supporting “medical home” services, according to Dr. Miller.
These efforts to create APMs that support high-quality, physician-directed care begin by identifying avoidable spending that varies from specialty to specialty and from condition to condition. Then they address barriers in the current fee-for-service system – such as no payment for many high-value services and insufficient revenue to cover costs when using fewer or low-cost services – by providing flexible, adequate payment while requiring physicians to take responsibility for the things they said could be avoidable when paid in that way. However, this responsibility must be focused on what a particular physician can influence, Mr. Miller noted.
Rheumatologists could be helped by these physician-focused payment models because they receive less than 10% of the total Medicare health care spending per patient whose care was directed by a rheumatologist. In that case, finding ways to drop total spending per patient by 5% could at the same time give rheumatologists a 25% increase in payment while also saving Medicare 3% overall, he said.
Rheumatologists are best set up to take condition-based payments that are geared to keep patients out of the hospital, rather than the hospital episode–based payments that have dominated APMs in existence so far. Central to this condition-based model is getting the right diagnosis at the start, so payment for getting the correct diagnosis would be critical.
APMs designed for rheumatologists could take into account the diseases often seen by a rheumatologist, such as RA, and then identify opportunities to improve care and reduce costs while identifying barriers in the current payment system for achieving those goals, Mr. Miller said. These opportunities and barriers would vary from condition to condition. In some cases, particularly for low-frequency conditions, there may not need to be a new payment model established and it could be done through fee-for-service.
Ideally, these condition-based payment models for specialists such as rheumatologists would exist within the “medical neighborhood” of primary care physicians who could refer to them when necessary. Specialists would be accountable for the aspects of care that they can control, such as avoiding unnecessary tests and procedures and avoiding infections and complications.
“That’s building the ACO from the bottom up, rather than what Medicare is trying to do, which is to create it from the top down,” Mr. Miller said.
Mr. Miller noted that it will be important for specialties such as rheumatology to define the cost data it needs in order to develop condition-based payment models.
Dr. Harvey had no relevant disclosures. Mr. Miller has no financial relationships with any commercial interests.
EXPERT ANALYSIS FROM THE ACR ANNUAL MEETING
MRI useful to distinguish between PACNS and neurosarcoidosis
WASHINGTON – MRI can help to differentiate between neurosarcoidosis and primary angiitis of the central nervous system, according to a single-center study comparing the two conditions.
Patients with neurosarcoidosis were significantly more likely to display spinal cord, basal meningeal, and cranial nerve involvements than were patients with primary angiitis of the central nervous system (PACNS), making MRI an efficient tool in distinguishing between the two.
Dr. Saygin and her coinvestigators at the Cleveland Clinic recruited 34 patients with PACNS and 42 patients with neurosarcoidosis, all of whom had brain and/or spinal cord MRIs performed close to the time of presentation. The average age was 45.6 years in the PACNS group and 44.1 years in the neurosarcoidosis group. The MRIs were blindly reviewed by two neuroradiologists who examined and recorded data on pachymeninges, leptomeninges, basal meninges, cranial nerves, cerebral gray and white matter, and the spinal cord itself. The sites, presence, patterns, localization, and lateral involvement for these were noted, as well as any mass effect, parenchymal hemorrhaging, and ventriculomegaly.
Unilateral cranial nerve involvement appeared on MRI in 71% of neurosarcoidosis patients, compared with 3.0% for PACNS. Neurosarcoidosis patients also had consistently higher rates of involvement of the spinal cord (cervical, 62.5% vs. 0%; thoracic, 45.8% vs. 0%) as well as basal meninges (basal cistern, 21.6% vs. 0%; brain stem, 27.0% vs. 3.0%).
However, there was no significant difference between PACNS and neurosarcoidosis patients in terms of the pachymeningeal and leptomeningeal involvement, pituitary/sella turcica involvement, and mass effect, the latter of which was seen in 20% of PACNS patients and 14% of those with neurosarcoidosis.
The relatively small sample size of 76 patients is a limitation of the study, Dr. Saygin said.
No funding source was disclosed for this study. Dr. Saygin did not report any relevant financial disclosures.
WASHINGTON – MRI can help to differentiate between neurosarcoidosis and primary angiitis of the central nervous system, according to a single-center study comparing the two conditions.
Patients with neurosarcoidosis were significantly more likely to display spinal cord, basal meningeal, and cranial nerve involvements than were patients with primary angiitis of the central nervous system (PACNS), making MRI an efficient tool in distinguishing between the two.
Dr. Saygin and her coinvestigators at the Cleveland Clinic recruited 34 patients with PACNS and 42 patients with neurosarcoidosis, all of whom had brain and/or spinal cord MRIs performed close to the time of presentation. The average age was 45.6 years in the PACNS group and 44.1 years in the neurosarcoidosis group. The MRIs were blindly reviewed by two neuroradiologists who examined and recorded data on pachymeninges, leptomeninges, basal meninges, cranial nerves, cerebral gray and white matter, and the spinal cord itself. The sites, presence, patterns, localization, and lateral involvement for these were noted, as well as any mass effect, parenchymal hemorrhaging, and ventriculomegaly.
Unilateral cranial nerve involvement appeared on MRI in 71% of neurosarcoidosis patients, compared with 3.0% for PACNS. Neurosarcoidosis patients also had consistently higher rates of involvement of the spinal cord (cervical, 62.5% vs. 0%; thoracic, 45.8% vs. 0%) as well as basal meninges (basal cistern, 21.6% vs. 0%; brain stem, 27.0% vs. 3.0%).
However, there was no significant difference between PACNS and neurosarcoidosis patients in terms of the pachymeningeal and leptomeningeal involvement, pituitary/sella turcica involvement, and mass effect, the latter of which was seen in 20% of PACNS patients and 14% of those with neurosarcoidosis.
The relatively small sample size of 76 patients is a limitation of the study, Dr. Saygin said.
No funding source was disclosed for this study. Dr. Saygin did not report any relevant financial disclosures.
WASHINGTON – MRI can help to differentiate between neurosarcoidosis and primary angiitis of the central nervous system, according to a single-center study comparing the two conditions.
Patients with neurosarcoidosis were significantly more likely to display spinal cord, basal meningeal, and cranial nerve involvements than were patients with primary angiitis of the central nervous system (PACNS), making MRI an efficient tool in distinguishing between the two.
Dr. Saygin and her coinvestigators at the Cleveland Clinic recruited 34 patients with PACNS and 42 patients with neurosarcoidosis, all of whom had brain and/or spinal cord MRIs performed close to the time of presentation. The average age was 45.6 years in the PACNS group and 44.1 years in the neurosarcoidosis group. The MRIs were blindly reviewed by two neuroradiologists who examined and recorded data on pachymeninges, leptomeninges, basal meninges, cranial nerves, cerebral gray and white matter, and the spinal cord itself. The sites, presence, patterns, localization, and lateral involvement for these were noted, as well as any mass effect, parenchymal hemorrhaging, and ventriculomegaly.
Unilateral cranial nerve involvement appeared on MRI in 71% of neurosarcoidosis patients, compared with 3.0% for PACNS. Neurosarcoidosis patients also had consistently higher rates of involvement of the spinal cord (cervical, 62.5% vs. 0%; thoracic, 45.8% vs. 0%) as well as basal meninges (basal cistern, 21.6% vs. 0%; brain stem, 27.0% vs. 3.0%).
However, there was no significant difference between PACNS and neurosarcoidosis patients in terms of the pachymeningeal and leptomeningeal involvement, pituitary/sella turcica involvement, and mass effect, the latter of which was seen in 20% of PACNS patients and 14% of those with neurosarcoidosis.
The relatively small sample size of 76 patients is a limitation of the study, Dr. Saygin said.
No funding source was disclosed for this study. Dr. Saygin did not report any relevant financial disclosures.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Unilateral cranial nerve involvement appeared on MRI in 71% of neurosarcoidosis patients, compared with 3.0% for PACNS.
Data source: Prospective cohort study of 34 PACNS patients and 42 neurosarcoidosis patients.
Disclosures: No relevant financial disclosures were reported.
Lupus patients may be shortchanged on lipid management
WASHINGTON – Many patients with systemic lupus erythematosus may not be getting lipid testing or statin prescriptions despite having risk factors and even frank cardiovascular conditions, according to a large Medicaid database study presented at the annual meeting of the American College of Rheumatology.
The study found that systemic lupus erythematosus (SLE) patients were half as likely to get a lipid screening and 77% less likely to get a statin prescription, compared with patients with diabetes, a group that has a similarly elevated baseline CV disease risk.
This is concerning because it has been shown in several studies that SLE patients have higher rates of CV events than do age- and sex-matched patients with diabetes, and hyperlipidemia has been associated with CV disease in SLE patients. However, no studies have directly demonstrated reduced CV disease risk with statin use in SLE patients, unlike the general population and in those with diabetes, and so no clear guidelines exist, said lead study author Sarah Chen, MD, a rheumatology fellow at Brigham and Women’s Hospital, Boston.
Analyses of 1 year of billing records for each patient showed that SLE patients visited their doctor significantly more often than did the diabetes patients during their index year (mean of 4.7 vs. 3.2 visits). They were more likely to have a renal manifestation of their disease (13% vs. 4%). Although hypertension was similar among lupus and diabetes patients (35% vs. 40%), lupus patients were less likely to have hyperlipidemia (11% vs. 24%) but more likely to have concurrent cardiovascular disease, defined as angina, heart attack, atherosclerosis, percutaneous coronary intervention, coronary artery bypass grafting, stroke, or peripheral artery disease (13% vs. 10%).
Overall, 27% of lupus patients and 42% of diabetes patients had at least one lipid screen during their study year. This proportion stayed steady among diabetes patients as they aged, but rose significantly among lupus patients from 23% in the youngest group of 18-39 years to 32% of the oldest group of 50-65 years.
“This suggests that diabetes patients are getting consistent cardiovascular assessment as they age, while lupus patients are not,” Dr. Chen said at the meeting.
Statin prescriptions were also significantly less common among lupus patients overall (12% vs. 33%). The proportion of lupus patients who got at least one statin prescription increased with age, from 7% in the youngest group to 21% in the oldest group. But it increased more among diabetes patients, from 23% among the youngest to 42% among the oldest, Dr. Chen noted.
She conducted a multivariate analysis that controlled for age, gender, race, ethnicity, region of residence, socioeconomic status, Charlson Comorbidity Index, and the presence of cardiovascular disease. This determined that lupus patients were 54% less likely to have lipid testing and 77% less likely to get a statin.
A subanalysis found some significant predictors of SLE patients’ receipt of lipid screening. Increasing age increased the odds of screening by 2% per year. Lipid screening was 6% more likely for each additional medication they took. Lupus patients with nephritis were 36% more likely to have a screening than were those without nephritis. Those with existing cardiovascular disease were 11% more likely to have a test than were those without it, although this odds ratio (OR) had a nonsignificant 95% confidence interval of 1.00-1.24.
Hispanic and Asian patients were significantly more likely to receive lipid testing than were whites.
A second subanalysis found significant predictors of lupus patients receiving a statin prescription among lupus patients. With every passing year, the chance of getting a statin increased by 5%; it also increased by 7% for every medication that a patient was taking. Being a male increased the likelihood of receiving a statin prescription by 23%. Lupus nephritis more than doubled the odds of getting a statin (OR, 2.34), and the presence of cardiovascular disease was a similarly strong predictor (OR, 1.95). Hispanics and Asians were more likely to get the medication than were whites.
One significant limitation of the study is a lack of results on lipid testing, particularly in light of the potential effect the results might have had on decisions to prescribe statins.
Dr. Chen had no financial disclosures. The study was supported by a grant from the National Institutes of Health.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Many patients with systemic lupus erythematosus may not be getting lipid testing or statin prescriptions despite having risk factors and even frank cardiovascular conditions, according to a large Medicaid database study presented at the annual meeting of the American College of Rheumatology.
The study found that systemic lupus erythematosus (SLE) patients were half as likely to get a lipid screening and 77% less likely to get a statin prescription, compared with patients with diabetes, a group that has a similarly elevated baseline CV disease risk.
This is concerning because it has been shown in several studies that SLE patients have higher rates of CV events than do age- and sex-matched patients with diabetes, and hyperlipidemia has been associated with CV disease in SLE patients. However, no studies have directly demonstrated reduced CV disease risk with statin use in SLE patients, unlike the general population and in those with diabetes, and so no clear guidelines exist, said lead study author Sarah Chen, MD, a rheumatology fellow at Brigham and Women’s Hospital, Boston.
Analyses of 1 year of billing records for each patient showed that SLE patients visited their doctor significantly more often than did the diabetes patients during their index year (mean of 4.7 vs. 3.2 visits). They were more likely to have a renal manifestation of their disease (13% vs. 4%). Although hypertension was similar among lupus and diabetes patients (35% vs. 40%), lupus patients were less likely to have hyperlipidemia (11% vs. 24%) but more likely to have concurrent cardiovascular disease, defined as angina, heart attack, atherosclerosis, percutaneous coronary intervention, coronary artery bypass grafting, stroke, or peripheral artery disease (13% vs. 10%).
Overall, 27% of lupus patients and 42% of diabetes patients had at least one lipid screen during their study year. This proportion stayed steady among diabetes patients as they aged, but rose significantly among lupus patients from 23% in the youngest group of 18-39 years to 32% of the oldest group of 50-65 years.
“This suggests that diabetes patients are getting consistent cardiovascular assessment as they age, while lupus patients are not,” Dr. Chen said at the meeting.
Statin prescriptions were also significantly less common among lupus patients overall (12% vs. 33%). The proportion of lupus patients who got at least one statin prescription increased with age, from 7% in the youngest group to 21% in the oldest group. But it increased more among diabetes patients, from 23% among the youngest to 42% among the oldest, Dr. Chen noted.
She conducted a multivariate analysis that controlled for age, gender, race, ethnicity, region of residence, socioeconomic status, Charlson Comorbidity Index, and the presence of cardiovascular disease. This determined that lupus patients were 54% less likely to have lipid testing and 77% less likely to get a statin.
A subanalysis found some significant predictors of SLE patients’ receipt of lipid screening. Increasing age increased the odds of screening by 2% per year. Lipid screening was 6% more likely for each additional medication they took. Lupus patients with nephritis were 36% more likely to have a screening than were those without nephritis. Those with existing cardiovascular disease were 11% more likely to have a test than were those without it, although this odds ratio (OR) had a nonsignificant 95% confidence interval of 1.00-1.24.
Hispanic and Asian patients were significantly more likely to receive lipid testing than were whites.
A second subanalysis found significant predictors of lupus patients receiving a statin prescription among lupus patients. With every passing year, the chance of getting a statin increased by 5%; it also increased by 7% for every medication that a patient was taking. Being a male increased the likelihood of receiving a statin prescription by 23%. Lupus nephritis more than doubled the odds of getting a statin (OR, 2.34), and the presence of cardiovascular disease was a similarly strong predictor (OR, 1.95). Hispanics and Asians were more likely to get the medication than were whites.
One significant limitation of the study is a lack of results on lipid testing, particularly in light of the potential effect the results might have had on decisions to prescribe statins.
Dr. Chen had no financial disclosures. The study was supported by a grant from the National Institutes of Health.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Many patients with systemic lupus erythematosus may not be getting lipid testing or statin prescriptions despite having risk factors and even frank cardiovascular conditions, according to a large Medicaid database study presented at the annual meeting of the American College of Rheumatology.
The study found that systemic lupus erythematosus (SLE) patients were half as likely to get a lipid screening and 77% less likely to get a statin prescription, compared with patients with diabetes, a group that has a similarly elevated baseline CV disease risk.
This is concerning because it has been shown in several studies that SLE patients have higher rates of CV events than do age- and sex-matched patients with diabetes, and hyperlipidemia has been associated with CV disease in SLE patients. However, no studies have directly demonstrated reduced CV disease risk with statin use in SLE patients, unlike the general population and in those with diabetes, and so no clear guidelines exist, said lead study author Sarah Chen, MD, a rheumatology fellow at Brigham and Women’s Hospital, Boston.
Analyses of 1 year of billing records for each patient showed that SLE patients visited their doctor significantly more often than did the diabetes patients during their index year (mean of 4.7 vs. 3.2 visits). They were more likely to have a renal manifestation of their disease (13% vs. 4%). Although hypertension was similar among lupus and diabetes patients (35% vs. 40%), lupus patients were less likely to have hyperlipidemia (11% vs. 24%) but more likely to have concurrent cardiovascular disease, defined as angina, heart attack, atherosclerosis, percutaneous coronary intervention, coronary artery bypass grafting, stroke, or peripheral artery disease (13% vs. 10%).
Overall, 27% of lupus patients and 42% of diabetes patients had at least one lipid screen during their study year. This proportion stayed steady among diabetes patients as they aged, but rose significantly among lupus patients from 23% in the youngest group of 18-39 years to 32% of the oldest group of 50-65 years.
“This suggests that diabetes patients are getting consistent cardiovascular assessment as they age, while lupus patients are not,” Dr. Chen said at the meeting.
Statin prescriptions were also significantly less common among lupus patients overall (12% vs. 33%). The proportion of lupus patients who got at least one statin prescription increased with age, from 7% in the youngest group to 21% in the oldest group. But it increased more among diabetes patients, from 23% among the youngest to 42% among the oldest, Dr. Chen noted.
She conducted a multivariate analysis that controlled for age, gender, race, ethnicity, region of residence, socioeconomic status, Charlson Comorbidity Index, and the presence of cardiovascular disease. This determined that lupus patients were 54% less likely to have lipid testing and 77% less likely to get a statin.
A subanalysis found some significant predictors of SLE patients’ receipt of lipid screening. Increasing age increased the odds of screening by 2% per year. Lipid screening was 6% more likely for each additional medication they took. Lupus patients with nephritis were 36% more likely to have a screening than were those without nephritis. Those with existing cardiovascular disease were 11% more likely to have a test than were those without it, although this odds ratio (OR) had a nonsignificant 95% confidence interval of 1.00-1.24.
Hispanic and Asian patients were significantly more likely to receive lipid testing than were whites.
A second subanalysis found significant predictors of lupus patients receiving a statin prescription among lupus patients. With every passing year, the chance of getting a statin increased by 5%; it also increased by 7% for every medication that a patient was taking. Being a male increased the likelihood of receiving a statin prescription by 23%. Lupus nephritis more than doubled the odds of getting a statin (OR, 2.34), and the presence of cardiovascular disease was a similarly strong predictor (OR, 1.95). Hispanics and Asians were more likely to get the medication than were whites.
One significant limitation of the study is a lack of results on lipid testing, particularly in light of the potential effect the results might have had on decisions to prescribe statins.
Dr. Chen had no financial disclosures. The study was supported by a grant from the National Institutes of Health.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Lupus patients were 54% less likely to have lipid level testing and 77% less likely to have a statin prescribed than were diabetes patients.
Data source: A Medicaid database review comprising nearly 20,000 lupus patients and 40,000 diabetes patients during 2007-2010.
Disclosures: Dr. Chen had no financial disclosures. The study was supported by a grant from the National Institutes of Health.
Tocilizumab raises cholesterol, but not cardiovascular events
WASHINGTON – The lipid changes induced by tocilizumab do not translate into an increased risk of heart attack or stroke in patients with rheumatoid arthritis, a 5-year postmarketing study has determined.
Patients taking the drug experienced quick and dramatic increases in low-density lipoprotein cholesterol: 12% in just 4 weeks. But when compared against patients taking etanercept, they showed no significant increases in stroke, heart attack, heart failure hospitalization, or cardiac death, Jon Giles, MD, said at the annual meeting of the American College of Rheumatology.
“This has been a lingering question,” he said. “These data are very reassuring. Practitioners can feel comfortable that they’re not inducing harm with this drug in patients with high cardiovascular risk. Now when we’re evaluating RA patients for the best drug, we can make a choice based on other parameters ... how the patient wants to take the drug, for example, or other safety indicators. This study takes away one element of uncertainty.”
Tocilizumab’s profound effects on lipids have been confirmed in all of its pivotal trials, with average across-the-board increases of 17%-25% in total cholesterol, low-and high-density cholesterol, and triglycerides. ENTRACTE is the first trial, however, to compare its cardiovascular safety profile to that of another RA medication.
The study comprised 3,080 patients with active, seropositive RA from 353 centers across 31 countries. The mean age of the patients was 61 years. All patients had at least one cardiovascular risk factor, including current smoking (30%), hypertension (71%), or diabetes (18%). About a quarter were already taking a statin, and about 5% had a history of heart attack, stroke, or coronary revascularization.
They were randomized to open-label tocilizumab 8 mg/kg infused every 4 weeks or etanercept 50 mg injected weekly. The mean follow-up reported was 3.5 years, but some patients had full 5-year data. “This was plenty of time to see early atherothrombotic complications if they were going to develop,” Dr. Giles said.
The primary endpoint was a composite of major cardiovascular outcomes including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included individual components of the primary endpoint, as well as all-cause mortality, heart failure hospitalization, fatal and nonfatal myocardial infarction and stroke, and lipid levels.
By week 4, LDL-cholesterol levels had risen by almost 12% in the tocilizumab group. This moderated somewhat, but stayed elevated, reaching 9% above baseline by week 144. In contrast, LDL-cholesterol in the etanercept group was virtually unchanged throughout the study.
In the intent-to-treat analysis, there were 161 occurrences of the composite outcome: 83 in the tocilizumab group and 78 in the etanercept group (hazard ratio, 1.05). This was not a significant difference. The event rate was 1.70 per 100 person-years in the etanercept group and 1.82 in the tocilizumab group – also not significantly different.
The individual secondary endpoints were almost identical in each group: cardiovascular death, 35 with etanercept vs. 36 with tocilizumab; nonfatal MI, 31 vs. 28; nonfatal stroke, 15 vs. 24; and all-cause mortality, 64 in each group. A multivariate regression analysis showed no significantly increased risks associated with tocilizumab in any of the secondary endpoints. The rates and types of adverse events were also similar.
Because this was a safety study, the investigators were interested in the uncertainty in their estimate of risk, Dr. Giles said in an interview.
“The study was designed to exclude at most an 80% increase in cardiovascular events for the patients treated with tocilizumab, compared with etanercept. What we determined was that we could exclude with 95% certainty that if a much larger sample of similar patients was studied, the risk of such events in the tocilizumab group would not exceed a 43% higher rate at the extreme. Notably, the degree of uncertainty included the possibility that the event rate could be lower in the tocilizumab group, compared with those treated with etanercept.”
Dr. Giles reported receiving consulting fees from Genentech, which markets tocilizumab. All other authors also disclosed financial relationships with Genentech or its parent company, Roche. Four authors were employees of Roche/Genentech.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – The lipid changes induced by tocilizumab do not translate into an increased risk of heart attack or stroke in patients with rheumatoid arthritis, a 5-year postmarketing study has determined.
Patients taking the drug experienced quick and dramatic increases in low-density lipoprotein cholesterol: 12% in just 4 weeks. But when compared against patients taking etanercept, they showed no significant increases in stroke, heart attack, heart failure hospitalization, or cardiac death, Jon Giles, MD, said at the annual meeting of the American College of Rheumatology.
“This has been a lingering question,” he said. “These data are very reassuring. Practitioners can feel comfortable that they’re not inducing harm with this drug in patients with high cardiovascular risk. Now when we’re evaluating RA patients for the best drug, we can make a choice based on other parameters ... how the patient wants to take the drug, for example, or other safety indicators. This study takes away one element of uncertainty.”
Tocilizumab’s profound effects on lipids have been confirmed in all of its pivotal trials, with average across-the-board increases of 17%-25% in total cholesterol, low-and high-density cholesterol, and triglycerides. ENTRACTE is the first trial, however, to compare its cardiovascular safety profile to that of another RA medication.
The study comprised 3,080 patients with active, seropositive RA from 353 centers across 31 countries. The mean age of the patients was 61 years. All patients had at least one cardiovascular risk factor, including current smoking (30%), hypertension (71%), or diabetes (18%). About a quarter were already taking a statin, and about 5% had a history of heart attack, stroke, or coronary revascularization.
They were randomized to open-label tocilizumab 8 mg/kg infused every 4 weeks or etanercept 50 mg injected weekly. The mean follow-up reported was 3.5 years, but some patients had full 5-year data. “This was plenty of time to see early atherothrombotic complications if they were going to develop,” Dr. Giles said.
The primary endpoint was a composite of major cardiovascular outcomes including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included individual components of the primary endpoint, as well as all-cause mortality, heart failure hospitalization, fatal and nonfatal myocardial infarction and stroke, and lipid levels.
By week 4, LDL-cholesterol levels had risen by almost 12% in the tocilizumab group. This moderated somewhat, but stayed elevated, reaching 9% above baseline by week 144. In contrast, LDL-cholesterol in the etanercept group was virtually unchanged throughout the study.
In the intent-to-treat analysis, there were 161 occurrences of the composite outcome: 83 in the tocilizumab group and 78 in the etanercept group (hazard ratio, 1.05). This was not a significant difference. The event rate was 1.70 per 100 person-years in the etanercept group and 1.82 in the tocilizumab group – also not significantly different.
The individual secondary endpoints were almost identical in each group: cardiovascular death, 35 with etanercept vs. 36 with tocilizumab; nonfatal MI, 31 vs. 28; nonfatal stroke, 15 vs. 24; and all-cause mortality, 64 in each group. A multivariate regression analysis showed no significantly increased risks associated with tocilizumab in any of the secondary endpoints. The rates and types of adverse events were also similar.
Because this was a safety study, the investigators were interested in the uncertainty in their estimate of risk, Dr. Giles said in an interview.
“The study was designed to exclude at most an 80% increase in cardiovascular events for the patients treated with tocilizumab, compared with etanercept. What we determined was that we could exclude with 95% certainty that if a much larger sample of similar patients was studied, the risk of such events in the tocilizumab group would not exceed a 43% higher rate at the extreme. Notably, the degree of uncertainty included the possibility that the event rate could be lower in the tocilizumab group, compared with those treated with etanercept.”
Dr. Giles reported receiving consulting fees from Genentech, which markets tocilizumab. All other authors also disclosed financial relationships with Genentech or its parent company, Roche. Four authors were employees of Roche/Genentech.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – The lipid changes induced by tocilizumab do not translate into an increased risk of heart attack or stroke in patients with rheumatoid arthritis, a 5-year postmarketing study has determined.
Patients taking the drug experienced quick and dramatic increases in low-density lipoprotein cholesterol: 12% in just 4 weeks. But when compared against patients taking etanercept, they showed no significant increases in stroke, heart attack, heart failure hospitalization, or cardiac death, Jon Giles, MD, said at the annual meeting of the American College of Rheumatology.
“This has been a lingering question,” he said. “These data are very reassuring. Practitioners can feel comfortable that they’re not inducing harm with this drug in patients with high cardiovascular risk. Now when we’re evaluating RA patients for the best drug, we can make a choice based on other parameters ... how the patient wants to take the drug, for example, or other safety indicators. This study takes away one element of uncertainty.”
Tocilizumab’s profound effects on lipids have been confirmed in all of its pivotal trials, with average across-the-board increases of 17%-25% in total cholesterol, low-and high-density cholesterol, and triglycerides. ENTRACTE is the first trial, however, to compare its cardiovascular safety profile to that of another RA medication.
The study comprised 3,080 patients with active, seropositive RA from 353 centers across 31 countries. The mean age of the patients was 61 years. All patients had at least one cardiovascular risk factor, including current smoking (30%), hypertension (71%), or diabetes (18%). About a quarter were already taking a statin, and about 5% had a history of heart attack, stroke, or coronary revascularization.
They were randomized to open-label tocilizumab 8 mg/kg infused every 4 weeks or etanercept 50 mg injected weekly. The mean follow-up reported was 3.5 years, but some patients had full 5-year data. “This was plenty of time to see early atherothrombotic complications if they were going to develop,” Dr. Giles said.
The primary endpoint was a composite of major cardiovascular outcomes including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included individual components of the primary endpoint, as well as all-cause mortality, heart failure hospitalization, fatal and nonfatal myocardial infarction and stroke, and lipid levels.
By week 4, LDL-cholesterol levels had risen by almost 12% in the tocilizumab group. This moderated somewhat, but stayed elevated, reaching 9% above baseline by week 144. In contrast, LDL-cholesterol in the etanercept group was virtually unchanged throughout the study.
In the intent-to-treat analysis, there were 161 occurrences of the composite outcome: 83 in the tocilizumab group and 78 in the etanercept group (hazard ratio, 1.05). This was not a significant difference. The event rate was 1.70 per 100 person-years in the etanercept group and 1.82 in the tocilizumab group – also not significantly different.
The individual secondary endpoints were almost identical in each group: cardiovascular death, 35 with etanercept vs. 36 with tocilizumab; nonfatal MI, 31 vs. 28; nonfatal stroke, 15 vs. 24; and all-cause mortality, 64 in each group. A multivariate regression analysis showed no significantly increased risks associated with tocilizumab in any of the secondary endpoints. The rates and types of adverse events were also similar.
Because this was a safety study, the investigators were interested in the uncertainty in their estimate of risk, Dr. Giles said in an interview.
“The study was designed to exclude at most an 80% increase in cardiovascular events for the patients treated with tocilizumab, compared with etanercept. What we determined was that we could exclude with 95% certainty that if a much larger sample of similar patients was studied, the risk of such events in the tocilizumab group would not exceed a 43% higher rate at the extreme. Notably, the degree of uncertainty included the possibility that the event rate could be lower in the tocilizumab group, compared with those treated with etanercept.”
Dr. Giles reported receiving consulting fees from Genentech, which markets tocilizumab. All other authors also disclosed financial relationships with Genentech or its parent company, Roche. Four authors were employees of Roche/Genentech.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: LDL-cholesterol levels rose by almost 12% in the tocilizumab group, but there was no corresponding increase in cardiovascular events.
Data source: ENTRACTE, which randomized 3,080 patients with RA to either tocilizumab or etanercept.
Disclosures: Dr. Giles reported receiving consulting fees from Genentech, which markets tocilizumab. All other authors also disclosed financial relationships with Genentech or its parent company, Roche. Four authors were employees of Roche/Genentech.
Prenatal exposure to TNF inhibitors does not increase infections in newborns
WASHINGTON – Prenatal exposure to tumor necrosis factor–inhibiting drugs does not significantly increase the risk of a serious antenatal infection in infants born to women taking the drugs for rheumatoid arthritis, according to a large database study.
Researchers from McGill University, Montreal, and the University of Alabama at Birmingham who conducted the study did find a higher rate of serious infections among infants born to users of a tumor necrosis factor inhibitor (TNFi), especially among those exposed to infliximab, but after adjustment for maternal age and other antirheumatic drugs, the risk was not statistically significant.
Infliximab is unique among the TNFi drugs in that it concentrates in cord blood, reaching levels that can exceed 150% of the maternal blood level, Dr. Vinet noted. Adalimumab concentrates similarly, although the current study did not find any significantly increased infection risk associated with that medication.
Dr. Vinet and her colleagues analyzed drug exposure in 2,455 infants born to mothers with rheumatoid arthritis (RA), who were included in the PregnAncies in RA mothers and Outcomes in offspring in the United States cohort (PAROUS) registry. This cohort is drawn from data in the national MarketScan commercial database. The infants were age- and gender-matched with more than 11,000 matched controls born to women without RA, and with no prenatal TNFi exposure. Among these drugs, she looked for exposure to adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab, as well as corticosteroids and other biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs).
Two exposures were considered: drugs taken during pregnancy and drugs taken before conception but not during pregnancy. These were compared with infants of mothers with RA who didn’t take TNFi drugs, and to the control infants. Serious infections were those that required a hospitalization during the first 12 months of life; only the index incident was counted.
Among the RA cohort, 290 (12%) were exposed to a TNFi during pregnancy and 109 (4%) were born to women who had taken a TNFi before conception. The remainder of the cohort was unexposed to those medications.
The mean maternal age was 32 years and similar in all RA categories and controls.
Corticosteroid use was common in women with RA, whether they took a TNFi during pregnancy (55%), before pregnancy (44%), or not at all (26%). Nonbiologic DMARDs were given to 19% of the TNFi cohort during pregnancy and 16% before pregnancy, as well as to 15% of those who didn’t take a TNFi.
The rate of serious neonatal infection was 2% among both infants born to RA mothers who didn’t take a TNFi and those born to RA mothers who took a TNFi before conception. Control infants born to women without RA had a serious infection rate of 0.2%.
Among infants exposed to a TNFi during pregnancy, the serious infection rate was 3%; it was also 3% among those exposed only in the third trimester.
A multivariate analysis that controlled for maternal age, prepregnancy diabetes, gestational diabetes, preterm birth, and exposure to the other drug categories determined that TNFi drugs did not significantly increase the risk of a serious infection in neonates with gestational exposure (odds ratio, 1.4) or whose mothers took the drugs before conception (OR, 0.9), compared with controls. The findings were similar when the analysis was restricted to TNFi exposure in the third trimester only.
When Dr. Vinet examined each drug independently, she found numerical differences in infection rates: golimumab and certolizumab pegol, 0%; adalimumab, 2.4%; etanercept 2.7%; and infliximab, 8.3%.
Because of the relatively small number of events, this portion of the regression analysis could not control for preterm birth and gestational diabetes. But after adjusting for maternal age and in utero corticosteroid exposure, Dr. Vinet found no significant associations with serious neonatal infection and any of the TNFi drugs, including infliximab (OR, 3.5; 95% CI, 0.8-15.0).
She and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Prenatal exposure to tumor necrosis factor–inhibiting drugs does not significantly increase the risk of a serious antenatal infection in infants born to women taking the drugs for rheumatoid arthritis, according to a large database study.
Researchers from McGill University, Montreal, and the University of Alabama at Birmingham who conducted the study did find a higher rate of serious infections among infants born to users of a tumor necrosis factor inhibitor (TNFi), especially among those exposed to infliximab, but after adjustment for maternal age and other antirheumatic drugs, the risk was not statistically significant.
Infliximab is unique among the TNFi drugs in that it concentrates in cord blood, reaching levels that can exceed 150% of the maternal blood level, Dr. Vinet noted. Adalimumab concentrates similarly, although the current study did not find any significantly increased infection risk associated with that medication.
Dr. Vinet and her colleagues analyzed drug exposure in 2,455 infants born to mothers with rheumatoid arthritis (RA), who were included in the PregnAncies in RA mothers and Outcomes in offspring in the United States cohort (PAROUS) registry. This cohort is drawn from data in the national MarketScan commercial database. The infants were age- and gender-matched with more than 11,000 matched controls born to women without RA, and with no prenatal TNFi exposure. Among these drugs, she looked for exposure to adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab, as well as corticosteroids and other biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs).
Two exposures were considered: drugs taken during pregnancy and drugs taken before conception but not during pregnancy. These were compared with infants of mothers with RA who didn’t take TNFi drugs, and to the control infants. Serious infections were those that required a hospitalization during the first 12 months of life; only the index incident was counted.
Among the RA cohort, 290 (12%) were exposed to a TNFi during pregnancy and 109 (4%) were born to women who had taken a TNFi before conception. The remainder of the cohort was unexposed to those medications.
The mean maternal age was 32 years and similar in all RA categories and controls.
Corticosteroid use was common in women with RA, whether they took a TNFi during pregnancy (55%), before pregnancy (44%), or not at all (26%). Nonbiologic DMARDs were given to 19% of the TNFi cohort during pregnancy and 16% before pregnancy, as well as to 15% of those who didn’t take a TNFi.
The rate of serious neonatal infection was 2% among both infants born to RA mothers who didn’t take a TNFi and those born to RA mothers who took a TNFi before conception. Control infants born to women without RA had a serious infection rate of 0.2%.
Among infants exposed to a TNFi during pregnancy, the serious infection rate was 3%; it was also 3% among those exposed only in the third trimester.
A multivariate analysis that controlled for maternal age, prepregnancy diabetes, gestational diabetes, preterm birth, and exposure to the other drug categories determined that TNFi drugs did not significantly increase the risk of a serious infection in neonates with gestational exposure (odds ratio, 1.4) or whose mothers took the drugs before conception (OR, 0.9), compared with controls. The findings were similar when the analysis was restricted to TNFi exposure in the third trimester only.
When Dr. Vinet examined each drug independently, she found numerical differences in infection rates: golimumab and certolizumab pegol, 0%; adalimumab, 2.4%; etanercept 2.7%; and infliximab, 8.3%.
Because of the relatively small number of events, this portion of the regression analysis could not control for preterm birth and gestational diabetes. But after adjusting for maternal age and in utero corticosteroid exposure, Dr. Vinet found no significant associations with serious neonatal infection and any of the TNFi drugs, including infliximab (OR, 3.5; 95% CI, 0.8-15.0).
She and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Prenatal exposure to tumor necrosis factor–inhibiting drugs does not significantly increase the risk of a serious antenatal infection in infants born to women taking the drugs for rheumatoid arthritis, according to a large database study.
Researchers from McGill University, Montreal, and the University of Alabama at Birmingham who conducted the study did find a higher rate of serious infections among infants born to users of a tumor necrosis factor inhibitor (TNFi), especially among those exposed to infliximab, but after adjustment for maternal age and other antirheumatic drugs, the risk was not statistically significant.
Infliximab is unique among the TNFi drugs in that it concentrates in cord blood, reaching levels that can exceed 150% of the maternal blood level, Dr. Vinet noted. Adalimumab concentrates similarly, although the current study did not find any significantly increased infection risk associated with that medication.
Dr. Vinet and her colleagues analyzed drug exposure in 2,455 infants born to mothers with rheumatoid arthritis (RA), who were included in the PregnAncies in RA mothers and Outcomes in offspring in the United States cohort (PAROUS) registry. This cohort is drawn from data in the national MarketScan commercial database. The infants were age- and gender-matched with more than 11,000 matched controls born to women without RA, and with no prenatal TNFi exposure. Among these drugs, she looked for exposure to adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab, as well as corticosteroids and other biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs).
Two exposures were considered: drugs taken during pregnancy and drugs taken before conception but not during pregnancy. These were compared with infants of mothers with RA who didn’t take TNFi drugs, and to the control infants. Serious infections were those that required a hospitalization during the first 12 months of life; only the index incident was counted.
Among the RA cohort, 290 (12%) were exposed to a TNFi during pregnancy and 109 (4%) were born to women who had taken a TNFi before conception. The remainder of the cohort was unexposed to those medications.
The mean maternal age was 32 years and similar in all RA categories and controls.
Corticosteroid use was common in women with RA, whether they took a TNFi during pregnancy (55%), before pregnancy (44%), or not at all (26%). Nonbiologic DMARDs were given to 19% of the TNFi cohort during pregnancy and 16% before pregnancy, as well as to 15% of those who didn’t take a TNFi.
The rate of serious neonatal infection was 2% among both infants born to RA mothers who didn’t take a TNFi and those born to RA mothers who took a TNFi before conception. Control infants born to women without RA had a serious infection rate of 0.2%.
Among infants exposed to a TNFi during pregnancy, the serious infection rate was 3%; it was also 3% among those exposed only in the third trimester.
A multivariate analysis that controlled for maternal age, prepregnancy diabetes, gestational diabetes, preterm birth, and exposure to the other drug categories determined that TNFi drugs did not significantly increase the risk of a serious infection in neonates with gestational exposure (odds ratio, 1.4) or whose mothers took the drugs before conception (OR, 0.9), compared with controls. The findings were similar when the analysis was restricted to TNFi exposure in the third trimester only.
When Dr. Vinet examined each drug independently, she found numerical differences in infection rates: golimumab and certolizumab pegol, 0%; adalimumab, 2.4%; etanercept 2.7%; and infliximab, 8.3%.
Because of the relatively small number of events, this portion of the regression analysis could not control for preterm birth and gestational diabetes. But after adjusting for maternal age and in utero corticosteroid exposure, Dr. Vinet found no significant associations with serious neonatal infection and any of the TNFi drugs, including infliximab (OR, 3.5; 95% CI, 0.8-15.0).
She and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The rates of serious neonatal infection were 2% among infants born to RA mothers without exposure to TNFi drugs and 3% among those exposed to the drugs during gestation.
Data source: The case-control study comprised 2,455 cases and more than 11,000 controls.
Disclosures: Dr. Vinet and her colleagues had no financial disclosures.
VIDEO: Ankylosing spondylitis problems outside the joints strike more women than men
WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.
Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.
The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”
In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.
They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.
Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.
Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).
Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.
In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).
Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.
Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.
The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”
In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.
They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.
Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.
Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).
Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.
In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).
Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.
Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.
The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”
In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.
They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.
Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.
Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).
Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.
In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).
Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Women were 70% more likely than men to develop an extra-articular manifestation of the disease.
Data source: The registry study comprised 564 patients.
Disclosures: Dr. Fitzgerald had no financial disclosures.
Sofosbuvir, daclatasvir combo best treatment for HCV cryoglobulinemia vasculitis
WASHINGTON – A combined regimen of sofosbuvir and daclatasvir is the best option to treat patients with hepatitis C virus infections experiencing cryoglobulinemia vasculitis, according to the findings of a new study presented at the annual meeting of the American College of Rheumatology.
“The HCV cryoglobulinemia vasculitis is a very important vasculitis because it represents 5% of chronically infected HCV patients in the world,” explained David Saadoun, MD, of Sorbonne Universities, Paris. “It’s sometimes a life-threatening vasculitis because patients may develop inflammation [so] there’s a need for very active and well-tolerated treatment.”
The primary endpoint – complete response to treatment at the end of the regimen – was achieved in 91% of subjects by the end of 24 weeks. Furthermore, 50% of patients experienced complete immunological response, defined as the complete clearance of cryoglobulin, within 24 weeks. At 12 weeks, average cryoglobulin levels decreased from 0.36 ± 0.12 to 0.10 ± 0.08 g/L, (P = .019), while average aminotransferase levels decreased from 57.6 ± 7.1 to 20.4 ± 2.0 IU/mL, (P less than .01).
But perhaps most significant, according to Dr. Saadoun, is that less than 5% of subjects required any additional treatment via immunosuppressants, such as steroids or rituximab. Average HCV viral loads dropped from 5.6 to 1.18 IU/mL at week 4 (P less than .01), with similarly sustained results through to week 12, indicating good virological responses. No serious adverse events were reported by any subjects throughout the trial period.
“The limitation is that there are quite a few patients, because it is only 35 patients this time, [and] that it’s a prospective, open-label study with no comparators,” Dr. Saadoun explained, adding that, in terms of further research, “[any] new study would focus on the way to avoid rituximab and steroid use in these patients, and to also have more patients treated with this regimen.”
No funding source was disclosed for this study. Dr. Saadoun did not report any relevant financial disclosures.
WASHINGTON – A combined regimen of sofosbuvir and daclatasvir is the best option to treat patients with hepatitis C virus infections experiencing cryoglobulinemia vasculitis, according to the findings of a new study presented at the annual meeting of the American College of Rheumatology.
“The HCV cryoglobulinemia vasculitis is a very important vasculitis because it represents 5% of chronically infected HCV patients in the world,” explained David Saadoun, MD, of Sorbonne Universities, Paris. “It’s sometimes a life-threatening vasculitis because patients may develop inflammation [so] there’s a need for very active and well-tolerated treatment.”
The primary endpoint – complete response to treatment at the end of the regimen – was achieved in 91% of subjects by the end of 24 weeks. Furthermore, 50% of patients experienced complete immunological response, defined as the complete clearance of cryoglobulin, within 24 weeks. At 12 weeks, average cryoglobulin levels decreased from 0.36 ± 0.12 to 0.10 ± 0.08 g/L, (P = .019), while average aminotransferase levels decreased from 57.6 ± 7.1 to 20.4 ± 2.0 IU/mL, (P less than .01).
But perhaps most significant, according to Dr. Saadoun, is that less than 5% of subjects required any additional treatment via immunosuppressants, such as steroids or rituximab. Average HCV viral loads dropped from 5.6 to 1.18 IU/mL at week 4 (P less than .01), with similarly sustained results through to week 12, indicating good virological responses. No serious adverse events were reported by any subjects throughout the trial period.
“The limitation is that there are quite a few patients, because it is only 35 patients this time, [and] that it’s a prospective, open-label study with no comparators,” Dr. Saadoun explained, adding that, in terms of further research, “[any] new study would focus on the way to avoid rituximab and steroid use in these patients, and to also have more patients treated with this regimen.”
No funding source was disclosed for this study. Dr. Saadoun did not report any relevant financial disclosures.
WASHINGTON – A combined regimen of sofosbuvir and daclatasvir is the best option to treat patients with hepatitis C virus infections experiencing cryoglobulinemia vasculitis, according to the findings of a new study presented at the annual meeting of the American College of Rheumatology.
“The HCV cryoglobulinemia vasculitis is a very important vasculitis because it represents 5% of chronically infected HCV patients in the world,” explained David Saadoun, MD, of Sorbonne Universities, Paris. “It’s sometimes a life-threatening vasculitis because patients may develop inflammation [so] there’s a need for very active and well-tolerated treatment.”
The primary endpoint – complete response to treatment at the end of the regimen – was achieved in 91% of subjects by the end of 24 weeks. Furthermore, 50% of patients experienced complete immunological response, defined as the complete clearance of cryoglobulin, within 24 weeks. At 12 weeks, average cryoglobulin levels decreased from 0.36 ± 0.12 to 0.10 ± 0.08 g/L, (P = .019), while average aminotransferase levels decreased from 57.6 ± 7.1 to 20.4 ± 2.0 IU/mL, (P less than .01).
But perhaps most significant, according to Dr. Saadoun, is that less than 5% of subjects required any additional treatment via immunosuppressants, such as steroids or rituximab. Average HCV viral loads dropped from 5.6 to 1.18 IU/mL at week 4 (P less than .01), with similarly sustained results through to week 12, indicating good virological responses. No serious adverse events were reported by any subjects throughout the trial period.
“The limitation is that there are quite a few patients, because it is only 35 patients this time, [and] that it’s a prospective, open-label study with no comparators,” Dr. Saadoun explained, adding that, in terms of further research, “[any] new study would focus on the way to avoid rituximab and steroid use in these patients, and to also have more patients treated with this regimen.”
No funding source was disclosed for this study. Dr. Saadoun did not report any relevant financial disclosures.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Of 35 patients, 32 (91%) achieved complete clinical response in 6 months, with less than 5% requiring the use of additional immunosuppressants and none experiencing serious adverse events.
Data source: A prospective, open-label study of 35 patients with cryoglobulinemia vasculitis brought on by HCV infection.
Disclosures: Dr. Saadoun did not report any relevant financial disclosures.
Prenatal exposure to hydroxychloroquine cuts risk of neonatal cutaneous lupus
WASHINGTON – Prenatal hydroxychloroquine reduces the risk of cutaneous neonatal lupus by 60% among the infants of women with a systemic autoimmune rheumatic disease.
The medication easily passes the placental barrier and confers significant protection to neonates born to women who have anti-Ro and anti-La antibodies, Julie Barsalou, MD, said at the annual meeting of the American College of Rheumatology.
Toll-like receptors 7 and 9 have been implicated in the initiation and maintenance of interface dermatitis, and hydroxychloroquine inhibits these receptors. In mouse studies, the drug has led to improvement of this type of dermatitis. Hydroxychloroquine also works well in treating subacute cutaneous lupus, she said, and because it can travel across the placenta, it could be an effective means of preventing this disorder in at-risk neonates.
To examine any potential benefit, Dr. Barsalou looked at three pediatric lupus databases: the SickKids NLE database from Toronto, the U.S. Research Registry for Neonatal Lupus, and the French Registry for Neonatal Lupus.
These registries include infants born to mothers with anti-Ro and/or anti-La antibodies, and a diagnosis of lupus, dermatomyositis, Sjögren’s syndrome, juvenile idiopathic arthritis, or rheumatic arthritis. No infants with cardiac neonatal lupus were included in the study.
In addition to hydroxychloroquine, Dr. Barsalou examined the use of prenatal azathioprine, nonfluorinated and fluorinated steroids, and intravenous immunoglobulin.
The cohort comprised 545 neonates born to 535 mothers. Among these, 112 developed cNLE. The remaining 433 infants were used as controls.
Mothers of both cases and controls were a mean age of 31 years. Among cases, the most common diagnosis was Sjögren’s syndrome (53%), followed by systemic lupus erythematosus (46%). Among controls, the most common maternal diagnosis was SLE (62%), followed by Sjögren’s (31%).
All mothers of cases were positive for anti-Ro antibodies; 72% were positive for anti-La antibodies. Among mothers of controls, 99% had anti-Ro antibodies and 48% had anti-La antibodies.
Mothers of cases took hydroxychloroquine (17%), fluorinated steroids (6%), and nonfluorinated steroids with or without azathioprine (28%). Mothers of controls took hydroxychloroquine (34%), fluorinated steroids (4%), and nonfluorinated steroids with or without azathioprine (44%),
There were significantly more female than male infants in the case group (65%). The median age at rash onset was 6 weeks.
Dr. Barsalou performed several multivariate analyses on the entire cohort, as well as two subgroup analyses: one on infants who developed the cNLE rash within the first 4 weeks of life and one on only the infants of mothers with SLE.
In the primary analysis, maternal anti-Ro and anti-La antibodies more than doubled the risk of an infant developing cNLE (odds ratio, 2.5). The use of hydroxychloroquine decreased this risk by 60% (OR, 0.4). Being a female infant increased the risk by 70% (OR, 1.7).
In the group of infants with early-onset rash, maternal anti-La antibodies more than tripled the risk (OR, 3.5), while the use of hydroxychloroquine decreased the risk by 80% (OR, 0.2).
Among the infants born to women with SLE, concomitant secondary Sjögren’s syndrome increased the risk of cNLE by more than threefold (OR, 3.5). Anti-La antibodies more than doubled the risk (OR, 2.5), and the use of hydroxychloroquine decreased it by 60% (OR, 0.4).
“This is the first study to address the prevention of cutaneous neonatal lupus,” Dr. Barsalou said. “We found that prenatal exposure to hydroxychloroquine is likely protective.”
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Prenatal hydroxychloroquine reduces the risk of cutaneous neonatal lupus by 60% among the infants of women with a systemic autoimmune rheumatic disease.
The medication easily passes the placental barrier and confers significant protection to neonates born to women who have anti-Ro and anti-La antibodies, Julie Barsalou, MD, said at the annual meeting of the American College of Rheumatology.
Toll-like receptors 7 and 9 have been implicated in the initiation and maintenance of interface dermatitis, and hydroxychloroquine inhibits these receptors. In mouse studies, the drug has led to improvement of this type of dermatitis. Hydroxychloroquine also works well in treating subacute cutaneous lupus, she said, and because it can travel across the placenta, it could be an effective means of preventing this disorder in at-risk neonates.
To examine any potential benefit, Dr. Barsalou looked at three pediatric lupus databases: the SickKids NLE database from Toronto, the U.S. Research Registry for Neonatal Lupus, and the French Registry for Neonatal Lupus.
These registries include infants born to mothers with anti-Ro and/or anti-La antibodies, and a diagnosis of lupus, dermatomyositis, Sjögren’s syndrome, juvenile idiopathic arthritis, or rheumatic arthritis. No infants with cardiac neonatal lupus were included in the study.
In addition to hydroxychloroquine, Dr. Barsalou examined the use of prenatal azathioprine, nonfluorinated and fluorinated steroids, and intravenous immunoglobulin.
The cohort comprised 545 neonates born to 535 mothers. Among these, 112 developed cNLE. The remaining 433 infants were used as controls.
Mothers of both cases and controls were a mean age of 31 years. Among cases, the most common diagnosis was Sjögren’s syndrome (53%), followed by systemic lupus erythematosus (46%). Among controls, the most common maternal diagnosis was SLE (62%), followed by Sjögren’s (31%).
All mothers of cases were positive for anti-Ro antibodies; 72% were positive for anti-La antibodies. Among mothers of controls, 99% had anti-Ro antibodies and 48% had anti-La antibodies.
Mothers of cases took hydroxychloroquine (17%), fluorinated steroids (6%), and nonfluorinated steroids with or without azathioprine (28%). Mothers of controls took hydroxychloroquine (34%), fluorinated steroids (4%), and nonfluorinated steroids with or without azathioprine (44%),
There were significantly more female than male infants in the case group (65%). The median age at rash onset was 6 weeks.
Dr. Barsalou performed several multivariate analyses on the entire cohort, as well as two subgroup analyses: one on infants who developed the cNLE rash within the first 4 weeks of life and one on only the infants of mothers with SLE.
In the primary analysis, maternal anti-Ro and anti-La antibodies more than doubled the risk of an infant developing cNLE (odds ratio, 2.5). The use of hydroxychloroquine decreased this risk by 60% (OR, 0.4). Being a female infant increased the risk by 70% (OR, 1.7).
In the group of infants with early-onset rash, maternal anti-La antibodies more than tripled the risk (OR, 3.5), while the use of hydroxychloroquine decreased the risk by 80% (OR, 0.2).
Among the infants born to women with SLE, concomitant secondary Sjögren’s syndrome increased the risk of cNLE by more than threefold (OR, 3.5). Anti-La antibodies more than doubled the risk (OR, 2.5), and the use of hydroxychloroquine decreased it by 60% (OR, 0.4).
“This is the first study to address the prevention of cutaneous neonatal lupus,” Dr. Barsalou said. “We found that prenatal exposure to hydroxychloroquine is likely protective.”
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Prenatal hydroxychloroquine reduces the risk of cutaneous neonatal lupus by 60% among the infants of women with a systemic autoimmune rheumatic disease.
The medication easily passes the placental barrier and confers significant protection to neonates born to women who have anti-Ro and anti-La antibodies, Julie Barsalou, MD, said at the annual meeting of the American College of Rheumatology.
Toll-like receptors 7 and 9 have been implicated in the initiation and maintenance of interface dermatitis, and hydroxychloroquine inhibits these receptors. In mouse studies, the drug has led to improvement of this type of dermatitis. Hydroxychloroquine also works well in treating subacute cutaneous lupus, she said, and because it can travel across the placenta, it could be an effective means of preventing this disorder in at-risk neonates.
To examine any potential benefit, Dr. Barsalou looked at three pediatric lupus databases: the SickKids NLE database from Toronto, the U.S. Research Registry for Neonatal Lupus, and the French Registry for Neonatal Lupus.
These registries include infants born to mothers with anti-Ro and/or anti-La antibodies, and a diagnosis of lupus, dermatomyositis, Sjögren’s syndrome, juvenile idiopathic arthritis, or rheumatic arthritis. No infants with cardiac neonatal lupus were included in the study.
In addition to hydroxychloroquine, Dr. Barsalou examined the use of prenatal azathioprine, nonfluorinated and fluorinated steroids, and intravenous immunoglobulin.
The cohort comprised 545 neonates born to 535 mothers. Among these, 112 developed cNLE. The remaining 433 infants were used as controls.
Mothers of both cases and controls were a mean age of 31 years. Among cases, the most common diagnosis was Sjögren’s syndrome (53%), followed by systemic lupus erythematosus (46%). Among controls, the most common maternal diagnosis was SLE (62%), followed by Sjögren’s (31%).
All mothers of cases were positive for anti-Ro antibodies; 72% were positive for anti-La antibodies. Among mothers of controls, 99% had anti-Ro antibodies and 48% had anti-La antibodies.
Mothers of cases took hydroxychloroquine (17%), fluorinated steroids (6%), and nonfluorinated steroids with or without azathioprine (28%). Mothers of controls took hydroxychloroquine (34%), fluorinated steroids (4%), and nonfluorinated steroids with or without azathioprine (44%),
There were significantly more female than male infants in the case group (65%). The median age at rash onset was 6 weeks.
Dr. Barsalou performed several multivariate analyses on the entire cohort, as well as two subgroup analyses: one on infants who developed the cNLE rash within the first 4 weeks of life and one on only the infants of mothers with SLE.
In the primary analysis, maternal anti-Ro and anti-La antibodies more than doubled the risk of an infant developing cNLE (odds ratio, 2.5). The use of hydroxychloroquine decreased this risk by 60% (OR, 0.4). Being a female infant increased the risk by 70% (OR, 1.7).
In the group of infants with early-onset rash, maternal anti-La antibodies more than tripled the risk (OR, 3.5), while the use of hydroxychloroquine decreased the risk by 80% (OR, 0.2).
Among the infants born to women with SLE, concomitant secondary Sjögren’s syndrome increased the risk of cNLE by more than threefold (OR, 3.5). Anti-La antibodies more than doubled the risk (OR, 2.5), and the use of hydroxychloroquine decreased it by 60% (OR, 0.4).
“This is the first study to address the prevention of cutaneous neonatal lupus,” Dr. Barsalou said. “We found that prenatal exposure to hydroxychloroquine is likely protective.”
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The drug was associated with a 60% decreased risk of developing the disorder.
Data source: The case-control study involved 545 infants.
Disclosures: Dr. Barsalou had no financial disclosures.
Low-dose cyclophosphamide unlikely to impair fertility in lupus patients
WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.
The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.
“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.
The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).
Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.
High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.
“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”
Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.
Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.
Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.
There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.
However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.
The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.
There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.
Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.
Dr. Tamirou and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.
The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.
“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.
The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).
Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.
High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.
“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”
Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.
Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.
Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.
There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.
However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.
The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.
There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.
Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.
Dr. Tamirou and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.
The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.
“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.
The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).
Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.
High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.
“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”
Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.
Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.
Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.
There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.
However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.
The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.
There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.
Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.
Dr. Tamirou and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Patients who got a cumulative cyclophosphamide dose of up to 6 grams had an anti-Mullerian hormone level close to 3 ng/mL, which is no different than the level in untreated patients.
Data source: The study comprised 155 women with systemic lupus erythematosus.
Disclosures: Dr. Tamirou and her colleagues had no financial disclosures.
Fiber may play role in lessening knee pain, OA development
Consumption of dietary fiber at the recommended average intake of 25 g per day was associated with lower risks of developing symptomatic knee osteoarthritis and moderate or severe knee pain over 4-8 years in two separate analyses of Osteoarthritis Initiative participants conducted by investigators at Boston University.
The studies are the first to describe an association between total dietary fiber and lower risk of symptomatic OA and pain worsening in the knee, as well as a lower risk of moderate and severe pain patterns. The lowered risks were partially mediated by body mass index (BMI) but persisted even after adjustment for the variable.
In both studies, the investigators estimated dietary fiber intake by using a validated food frequency questionnaire at baseline that summed the fibers from grains, fruits and vegetables, and nuts and legumes.
Fiber and symptomatic knee OA
At the end of 4 years of follow-up, Dr. Dai and her colleagues identified 152 knees with incident radiographic OA (defined as a knee newly developing a Kellgren and Lawrence grade of 2 or higher), 869 knees with incident symptomatic OA (defined as new onset of both radiographic OA and a painful knee on most days in past month), and 1,964 knees with pain worsening as defined by an increase of at least 14% of the baseline Western Ontario and McMaster Universities (WOMAC) Index pain subscale score at each annual exam. This analysis excluded 540 people who were lost to follow-up and 205 who had invalid caloric intake recordings, leaving 4,051 in the study. The outcomes also excluded people with prevalent radiographic or symptomatic knee OA or knee pain worsening at baseline.
There was a significant trend for lower risk of both symptomatic OA (P less than .002) and pain worsening (P = .005) across four quartiles of daily total dietary fiber intake (mean of 9.1 g, 13 g, 16 g, and 21.9 g in quartiles 1-4). Quartile 4 daily intake was associated with a statistically significant 30% reduction (95% confidence interval, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening. Both comparisons were adjusted for age, sex, race, total energy intake, education, smoking status, physical activity, intake of other dietary factors (including polyunsaturated fat and other fats, vitamin C, vitamin D, vitamin E, vitamin K, dairy products, sweets, and soda), and nonsteroidal anti-inflammatory drug use (for the pain-worsening comparison).
Even though approximately 34% of the association between total fiber intake and symptomatic OA and 22% of the association between total fiber intake and pain worsening were mediated through reduced BMI, further adjustment of the comparisons for baseline BMI yielded similarly significant results.
The investigators found no associations between total dietary fiber intake and radiographic knee OA or for other fiber intake with either symptomatic or radiographic knee OA.
“The strongest protection was suggested at the highest quartile, which is in line with the current dietary guidelines for daily fiber intake. For older people [aged 51 years and older], for women it’s 22 g per day and for men it’s 28 g per day,” Dr. Dai said at the meeting.
Fiber and knee pain trajectories
Dr. Dai and her associates identified distinct, relatively homogeneous clusters of WOMAC pain trajectories over the 8-year study course in patients with and without radiographic knee OA at baseline in the Arthritis Care & Research study, and then examined their relationship to participants’ total dietary fiber intake, divided into quartiles (Arthritis Res Care. 2016; Nov 29. doi: 10.1002/acr.23158). The investigators found four pain trajectory patterns, including no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%).
Individuals who consumed the most total fiber also had the highest representation in the no pain pattern (38.1%) and the lowest representation in the severe pain pattern (4.3%). A high total fiber intake was associated with lower risk of having a moderate or severe pain pattern when compared with those in the no pain trajectory (both P for trend less than .01). Intake of fiber in the highest quartile was associated with a 24% lower likelihood (95% CI, 7%-39%) of belonging to the moderate pain pattern and a 44% lower likelihood (95% CI, 2%-59%) of being in the severe pain pattern, compared with individuals in the lowest intake quartile.
The same four pain trajectory patterns existed in individuals with radiographic knee OA at baseline, but the proportions were shifted slightly lower for no pain (26.1%) and higher for severe pain (7.9%). There was an even greater effect magnitude for the association between dietary total fiber and moderate or severe pain pattern among individuals with radiographic knee OA at baseline. Similar results were found for participants without radiographic knee OA at baseline. The relationships between total dietary fiber intake and pain patterns were somewhat attenuated after adjustment for depression scores and BMI at baseline but still remained statistically significant.
In each of the comparisons and sensitivity analyses, the highest quartile of cereal grain fiber intake was also significant on its own in lowering risk for being in the moderate or severe pain trajectory patterns. However, no significant results were found for fiber from fruits and vegetables or from nuts and legumes.
The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
Consumption of dietary fiber at the recommended average intake of 25 g per day was associated with lower risks of developing symptomatic knee osteoarthritis and moderate or severe knee pain over 4-8 years in two separate analyses of Osteoarthritis Initiative participants conducted by investigators at Boston University.
The studies are the first to describe an association between total dietary fiber and lower risk of symptomatic OA and pain worsening in the knee, as well as a lower risk of moderate and severe pain patterns. The lowered risks were partially mediated by body mass index (BMI) but persisted even after adjustment for the variable.
In both studies, the investigators estimated dietary fiber intake by using a validated food frequency questionnaire at baseline that summed the fibers from grains, fruits and vegetables, and nuts and legumes.
Fiber and symptomatic knee OA
At the end of 4 years of follow-up, Dr. Dai and her colleagues identified 152 knees with incident radiographic OA (defined as a knee newly developing a Kellgren and Lawrence grade of 2 or higher), 869 knees with incident symptomatic OA (defined as new onset of both radiographic OA and a painful knee on most days in past month), and 1,964 knees with pain worsening as defined by an increase of at least 14% of the baseline Western Ontario and McMaster Universities (WOMAC) Index pain subscale score at each annual exam. This analysis excluded 540 people who were lost to follow-up and 205 who had invalid caloric intake recordings, leaving 4,051 in the study. The outcomes also excluded people with prevalent radiographic or symptomatic knee OA or knee pain worsening at baseline.
There was a significant trend for lower risk of both symptomatic OA (P less than .002) and pain worsening (P = .005) across four quartiles of daily total dietary fiber intake (mean of 9.1 g, 13 g, 16 g, and 21.9 g in quartiles 1-4). Quartile 4 daily intake was associated with a statistically significant 30% reduction (95% confidence interval, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening. Both comparisons were adjusted for age, sex, race, total energy intake, education, smoking status, physical activity, intake of other dietary factors (including polyunsaturated fat and other fats, vitamin C, vitamin D, vitamin E, vitamin K, dairy products, sweets, and soda), and nonsteroidal anti-inflammatory drug use (for the pain-worsening comparison).
Even though approximately 34% of the association between total fiber intake and symptomatic OA and 22% of the association between total fiber intake and pain worsening were mediated through reduced BMI, further adjustment of the comparisons for baseline BMI yielded similarly significant results.
The investigators found no associations between total dietary fiber intake and radiographic knee OA or for other fiber intake with either symptomatic or radiographic knee OA.
“The strongest protection was suggested at the highest quartile, which is in line with the current dietary guidelines for daily fiber intake. For older people [aged 51 years and older], for women it’s 22 g per day and for men it’s 28 g per day,” Dr. Dai said at the meeting.
Fiber and knee pain trajectories
Dr. Dai and her associates identified distinct, relatively homogeneous clusters of WOMAC pain trajectories over the 8-year study course in patients with and without radiographic knee OA at baseline in the Arthritis Care & Research study, and then examined their relationship to participants’ total dietary fiber intake, divided into quartiles (Arthritis Res Care. 2016; Nov 29. doi: 10.1002/acr.23158). The investigators found four pain trajectory patterns, including no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%).
Individuals who consumed the most total fiber also had the highest representation in the no pain pattern (38.1%) and the lowest representation in the severe pain pattern (4.3%). A high total fiber intake was associated with lower risk of having a moderate or severe pain pattern when compared with those in the no pain trajectory (both P for trend less than .01). Intake of fiber in the highest quartile was associated with a 24% lower likelihood (95% CI, 7%-39%) of belonging to the moderate pain pattern and a 44% lower likelihood (95% CI, 2%-59%) of being in the severe pain pattern, compared with individuals in the lowest intake quartile.
The same four pain trajectory patterns existed in individuals with radiographic knee OA at baseline, but the proportions were shifted slightly lower for no pain (26.1%) and higher for severe pain (7.9%). There was an even greater effect magnitude for the association between dietary total fiber and moderate or severe pain pattern among individuals with radiographic knee OA at baseline. Similar results were found for participants without radiographic knee OA at baseline. The relationships between total dietary fiber intake and pain patterns were somewhat attenuated after adjustment for depression scores and BMI at baseline but still remained statistically significant.
In each of the comparisons and sensitivity analyses, the highest quartile of cereal grain fiber intake was also significant on its own in lowering risk for being in the moderate or severe pain trajectory patterns. However, no significant results were found for fiber from fruits and vegetables or from nuts and legumes.
The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
Consumption of dietary fiber at the recommended average intake of 25 g per day was associated with lower risks of developing symptomatic knee osteoarthritis and moderate or severe knee pain over 4-8 years in two separate analyses of Osteoarthritis Initiative participants conducted by investigators at Boston University.
The studies are the first to describe an association between total dietary fiber and lower risk of symptomatic OA and pain worsening in the knee, as well as a lower risk of moderate and severe pain patterns. The lowered risks were partially mediated by body mass index (BMI) but persisted even after adjustment for the variable.
In both studies, the investigators estimated dietary fiber intake by using a validated food frequency questionnaire at baseline that summed the fibers from grains, fruits and vegetables, and nuts and legumes.
Fiber and symptomatic knee OA
At the end of 4 years of follow-up, Dr. Dai and her colleagues identified 152 knees with incident radiographic OA (defined as a knee newly developing a Kellgren and Lawrence grade of 2 or higher), 869 knees with incident symptomatic OA (defined as new onset of both radiographic OA and a painful knee on most days in past month), and 1,964 knees with pain worsening as defined by an increase of at least 14% of the baseline Western Ontario and McMaster Universities (WOMAC) Index pain subscale score at each annual exam. This analysis excluded 540 people who were lost to follow-up and 205 who had invalid caloric intake recordings, leaving 4,051 in the study. The outcomes also excluded people with prevalent radiographic or symptomatic knee OA or knee pain worsening at baseline.
There was a significant trend for lower risk of both symptomatic OA (P less than .002) and pain worsening (P = .005) across four quartiles of daily total dietary fiber intake (mean of 9.1 g, 13 g, 16 g, and 21.9 g in quartiles 1-4). Quartile 4 daily intake was associated with a statistically significant 30% reduction (95% confidence interval, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening. Both comparisons were adjusted for age, sex, race, total energy intake, education, smoking status, physical activity, intake of other dietary factors (including polyunsaturated fat and other fats, vitamin C, vitamin D, vitamin E, vitamin K, dairy products, sweets, and soda), and nonsteroidal anti-inflammatory drug use (for the pain-worsening comparison).
Even though approximately 34% of the association between total fiber intake and symptomatic OA and 22% of the association between total fiber intake and pain worsening were mediated through reduced BMI, further adjustment of the comparisons for baseline BMI yielded similarly significant results.
The investigators found no associations between total dietary fiber intake and radiographic knee OA or for other fiber intake with either symptomatic or radiographic knee OA.
“The strongest protection was suggested at the highest quartile, which is in line with the current dietary guidelines for daily fiber intake. For older people [aged 51 years and older], for women it’s 22 g per day and for men it’s 28 g per day,” Dr. Dai said at the meeting.
Fiber and knee pain trajectories
Dr. Dai and her associates identified distinct, relatively homogeneous clusters of WOMAC pain trajectories over the 8-year study course in patients with and without radiographic knee OA at baseline in the Arthritis Care & Research study, and then examined their relationship to participants’ total dietary fiber intake, divided into quartiles (Arthritis Res Care. 2016; Nov 29. doi: 10.1002/acr.23158). The investigators found four pain trajectory patterns, including no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%).
Individuals who consumed the most total fiber also had the highest representation in the no pain pattern (38.1%) and the lowest representation in the severe pain pattern (4.3%). A high total fiber intake was associated with lower risk of having a moderate or severe pain pattern when compared with those in the no pain trajectory (both P for trend less than .01). Intake of fiber in the highest quartile was associated with a 24% lower likelihood (95% CI, 7%-39%) of belonging to the moderate pain pattern and a 44% lower likelihood (95% CI, 2%-59%) of being in the severe pain pattern, compared with individuals in the lowest intake quartile.
The same four pain trajectory patterns existed in individuals with radiographic knee OA at baseline, but the proportions were shifted slightly lower for no pain (26.1%) and higher for severe pain (7.9%). There was an even greater effect magnitude for the association between dietary total fiber and moderate or severe pain pattern among individuals with radiographic knee OA at baseline. Similar results were found for participants without radiographic knee OA at baseline. The relationships between total dietary fiber intake and pain patterns were somewhat attenuated after adjustment for depression scores and BMI at baseline but still remained statistically significant.
In each of the comparisons and sensitivity analyses, the highest quartile of cereal grain fiber intake was also significant on its own in lowering risk for being in the moderate or severe pain trajectory patterns. However, no significant results were found for fiber from fruits and vegetables or from nuts and legumes.
The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.
FROM ARTHRITIS CARE & RESEARCH AND THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The highest quartile of daily dietary fiber intake was associated with a statistically significant 30% reduction (95% CI, 6%-48%) in the odds of symptomatic knee OA and a 19% reduction (95% CI, 6%-29%) in the odds of pain worsening.
Data source: Two analyses of the prospective, multicenter Osteoarthritis Initiative cohort of 4,796 men and women aged 45-79 years with or at risk for knee osteoarthritis.
Disclosures: The studies were supported by grants from the National Institutes of Health. None of the authors had conflicts of interest to disclose.