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Stroke policy recommendations incorporate advances in endovascular therapy
Stroke centers need to collaborate within their regions to assure best practices and optimal access to comprehensive stroke centers as well as newly-designated thrombectomy-capable stroke centers, according to an updated policy statement from the American Stroke Association published in Stroke.
Opeolu Adeoye, MD, associate professor of emergency medicine and neurosurgery at the University of Cincinnati – and chair of the policy statement writing group – and coauthors updated the ASA’s 2005 recommendations for policy makers and public health care agencies to reflect current evidence, the increased availability of endovascular therapy, and new stroke center certifications.
“We have seen monumental advancements in acute stroke care over the past 14 years, and our concept of a comprehensive stroke system of care has evolved as a result,” Dr. Adeoye said in a news release.
While a recommendation to support the initiation of stroke prevention regimens remains unchanged from the 2005 recommendations, the 2019 update emphasizes a need to support long-term adherence to such regimens. To that end, researchers should examine the potential benefits of stroke prevention efforts that incorporate social media, gamification, and other technologies and principles to promote healthy behavior, the authors suggested. Furthermore, technology may allow for the passive surveillance of baseline behaviors and enable researchers to track changes in behavior over time.
Thrombectomy-capable centers
Thrombectomy-capable stroke centers, which have capabilities between those of primary stroke centers and comprehensive stroke centers, provide a relatively new level of acute stroke care. In communities that do not otherwise have access to thrombectomy, these centers play a clear role. In communities with comprehensive stroke centers, their role “is more controversial, and routing plans for patients with a suspected LVO [large vessel occlusion] should always seek the center of highest capability when travel time differences are short,” the statement says.
Timely parenchymal and arterial imaging via CT or MRI are needed to identify the subset of patients who may benefit from thrombectomy. All centers managing stroke patients should develop a plan for the definitive identification and treatment of these patients. Imaging techniques that assess penumbral patterns to identify candidates for endovascular therapy between 6 and 24 hours after patients were last known to be normal “merit broader adoption,” the statement says.
Hospitals without thrombectomy capability should have transfer protocols to allow the rapid treatment of these patients to hospitals with the appropriate level of care. In rural facilities that lack 24/7 imaging and radiology capabilities, this may mean rapid transfer of patients with clinically suspected LVO to hospitals where their work-up may be expedited.
To improve process, centers providing thrombectomy should rigorously track patient flow at all time points from presentation to imaging to intervention. Reperfusion rates, procedural complications, and patient clinical outcomes must be tracked and reported.
Travel times
Triage paradigms and protocols should be developed to ensure that emergency medical service (EMS) providers are able to rapidly identify all patients with a known or suspected stroke and to assess them with a validated and standardized instrument for stroke screening such as FAST (Face, Arm, Speech, Time), Los Angeles Prehospital Stroke Screen, or Cincinnati Prehospital Stroke Scale.
In prehospital patients who screen positive for suspected stroke, a standard prehospital stroke severity assessment tool such as the Cincinnati Stroke Triage Assessment Tool, Rapid Arterial Occlusion Evaluation, Los Angeles Motor Scale, or Field Assessment Stroke Triage for Emergency Destination should be used. “Further research is needed to establish the most effective prehospital stroke severity triage scale,” the authors noted. In all cases, EMS should notify hospitals that a stroke patient is en route.
“When there are several intravenous alteplase–capable hospitals in a well-defined geographic region, extra transportation times to reach a facility capable of endovascular thrombectomy should be limited to no more than 15 minutes in patients with a prehospital stroke severity score suggestive of LVO,” according to the recommendations. “When several hospital options exist within similar travel times, EMS should seek care at the facility capable of offering the highest level of stroke care. Further research is needed to establish travel time parameters for hospital bypass in cases of prehospital suspicion of LVO.”
Outcomes and discharge
Centers should track various treatment and patient outcomes, and all patients discharged to their homes should have appropriate follow-up with specialized stroke services and primary care and be screened for postacute complications.
Government institutions should standardize the organization of stroke care, ensure that stroke patients receive timely care at appropriate hospitals, and facilitate access to secondary prevention and rehabilitation resources after stroke, the authors wrote.
“Programs geared at further improving the knowledge of the public, encouraging primordial and primary prevention, advancing and facilitating acute therapy, improving secondary prevention and recovery from stroke, and reducing disparities in stroke care should be actively developed in a coordinated and collaborative fashion by providers and policymakers at the local, state, and national levels,” the authors concluded. “Such efforts will continue to mitigate the effects of stroke on society.”
Dr. Adeoye had no disclosures. Some coauthors reported research grants and consultant or advisory board positions.
SOURCE: Adeoye O et al. Stroke. 2019 May 20. doi: 10.1161/STR.0000000000000173.
When determining where to transport a patient with stroke, uncertainty about the patient’s diagnosis and eligibility for thrombectomy is a necessary consideration, said Robert A. Harrington, MD, of Stanford University (Calif.), in an accompanying editorial.
In lieu of better data, stroke systems should follow the recommendation of the Mission: Lifeline Severity-based Stroke Triage Algorithm for emergency medical services to avoid more than 15 minutes of additional travel time to transport a patient to a center that can perform endovascular therapy when the patient may be eligible for intravenous tissue plasminogen activator (tPA), said Dr. Harrington.
Delays in initiating tPA could lead to some patients not receiving treatment. “Some patients with suspected LVO [large vessel occlusion] either will not have thrombectomy or will not be eligible for it, and they also run the risk of not receiving any acute reperfusion therapy. Consequently, transport algorithms and models must take into account the uncertainty in prehospital diagnosis when considering the most appropriate facility,” he said.
Forthcoming acute stroke guidelines “will recommend intravenous tPA for all eligible subjects” because administration of tPA before endovascular thrombectomy does not appear to be harmful, Dr. Harrington noted.
Ultimately, approaches to routing patients may vary by region. “It is up to local and regional communities ... to define how best to implement these elements into a stroke system of care that meets their needs and resources and to define the types of hospitals that should qualify as points of entry for patients with suspected LVO strokes,” Dr. Harrington said.
A group convened by the American Heart Association and American Stroke Association is drafting further guiding principles for stroke systems of care in various regional settings.
Dr. Harrington is president-elect of the American Heart Association. He reported receiving research grants from AstraZeneca and Bristol-Myers Squibb.
When determining where to transport a patient with stroke, uncertainty about the patient’s diagnosis and eligibility for thrombectomy is a necessary consideration, said Robert A. Harrington, MD, of Stanford University (Calif.), in an accompanying editorial.
In lieu of better data, stroke systems should follow the recommendation of the Mission: Lifeline Severity-based Stroke Triage Algorithm for emergency medical services to avoid more than 15 minutes of additional travel time to transport a patient to a center that can perform endovascular therapy when the patient may be eligible for intravenous tissue plasminogen activator (tPA), said Dr. Harrington.
Delays in initiating tPA could lead to some patients not receiving treatment. “Some patients with suspected LVO [large vessel occlusion] either will not have thrombectomy or will not be eligible for it, and they also run the risk of not receiving any acute reperfusion therapy. Consequently, transport algorithms and models must take into account the uncertainty in prehospital diagnosis when considering the most appropriate facility,” he said.
Forthcoming acute stroke guidelines “will recommend intravenous tPA for all eligible subjects” because administration of tPA before endovascular thrombectomy does not appear to be harmful, Dr. Harrington noted.
Ultimately, approaches to routing patients may vary by region. “It is up to local and regional communities ... to define how best to implement these elements into a stroke system of care that meets their needs and resources and to define the types of hospitals that should qualify as points of entry for patients with suspected LVO strokes,” Dr. Harrington said.
A group convened by the American Heart Association and American Stroke Association is drafting further guiding principles for stroke systems of care in various regional settings.
Dr. Harrington is president-elect of the American Heart Association. He reported receiving research grants from AstraZeneca and Bristol-Myers Squibb.
When determining where to transport a patient with stroke, uncertainty about the patient’s diagnosis and eligibility for thrombectomy is a necessary consideration, said Robert A. Harrington, MD, of Stanford University (Calif.), in an accompanying editorial.
In lieu of better data, stroke systems should follow the recommendation of the Mission: Lifeline Severity-based Stroke Triage Algorithm for emergency medical services to avoid more than 15 minutes of additional travel time to transport a patient to a center that can perform endovascular therapy when the patient may be eligible for intravenous tissue plasminogen activator (tPA), said Dr. Harrington.
Delays in initiating tPA could lead to some patients not receiving treatment. “Some patients with suspected LVO [large vessel occlusion] either will not have thrombectomy or will not be eligible for it, and they also run the risk of not receiving any acute reperfusion therapy. Consequently, transport algorithms and models must take into account the uncertainty in prehospital diagnosis when considering the most appropriate facility,” he said.
Forthcoming acute stroke guidelines “will recommend intravenous tPA for all eligible subjects” because administration of tPA before endovascular thrombectomy does not appear to be harmful, Dr. Harrington noted.
Ultimately, approaches to routing patients may vary by region. “It is up to local and regional communities ... to define how best to implement these elements into a stroke system of care that meets their needs and resources and to define the types of hospitals that should qualify as points of entry for patients with suspected LVO strokes,” Dr. Harrington said.
A group convened by the American Heart Association and American Stroke Association is drafting further guiding principles for stroke systems of care in various regional settings.
Dr. Harrington is president-elect of the American Heart Association. He reported receiving research grants from AstraZeneca and Bristol-Myers Squibb.
Stroke centers need to collaborate within their regions to assure best practices and optimal access to comprehensive stroke centers as well as newly-designated thrombectomy-capable stroke centers, according to an updated policy statement from the American Stroke Association published in Stroke.
Opeolu Adeoye, MD, associate professor of emergency medicine and neurosurgery at the University of Cincinnati – and chair of the policy statement writing group – and coauthors updated the ASA’s 2005 recommendations for policy makers and public health care agencies to reflect current evidence, the increased availability of endovascular therapy, and new stroke center certifications.
“We have seen monumental advancements in acute stroke care over the past 14 years, and our concept of a comprehensive stroke system of care has evolved as a result,” Dr. Adeoye said in a news release.
While a recommendation to support the initiation of stroke prevention regimens remains unchanged from the 2005 recommendations, the 2019 update emphasizes a need to support long-term adherence to such regimens. To that end, researchers should examine the potential benefits of stroke prevention efforts that incorporate social media, gamification, and other technologies and principles to promote healthy behavior, the authors suggested. Furthermore, technology may allow for the passive surveillance of baseline behaviors and enable researchers to track changes in behavior over time.
Thrombectomy-capable centers
Thrombectomy-capable stroke centers, which have capabilities between those of primary stroke centers and comprehensive stroke centers, provide a relatively new level of acute stroke care. In communities that do not otherwise have access to thrombectomy, these centers play a clear role. In communities with comprehensive stroke centers, their role “is more controversial, and routing plans for patients with a suspected LVO [large vessel occlusion] should always seek the center of highest capability when travel time differences are short,” the statement says.
Timely parenchymal and arterial imaging via CT or MRI are needed to identify the subset of patients who may benefit from thrombectomy. All centers managing stroke patients should develop a plan for the definitive identification and treatment of these patients. Imaging techniques that assess penumbral patterns to identify candidates for endovascular therapy between 6 and 24 hours after patients were last known to be normal “merit broader adoption,” the statement says.
Hospitals without thrombectomy capability should have transfer protocols to allow the rapid treatment of these patients to hospitals with the appropriate level of care. In rural facilities that lack 24/7 imaging and radiology capabilities, this may mean rapid transfer of patients with clinically suspected LVO to hospitals where their work-up may be expedited.
To improve process, centers providing thrombectomy should rigorously track patient flow at all time points from presentation to imaging to intervention. Reperfusion rates, procedural complications, and patient clinical outcomes must be tracked and reported.
Travel times
Triage paradigms and protocols should be developed to ensure that emergency medical service (EMS) providers are able to rapidly identify all patients with a known or suspected stroke and to assess them with a validated and standardized instrument for stroke screening such as FAST (Face, Arm, Speech, Time), Los Angeles Prehospital Stroke Screen, or Cincinnati Prehospital Stroke Scale.
In prehospital patients who screen positive for suspected stroke, a standard prehospital stroke severity assessment tool such as the Cincinnati Stroke Triage Assessment Tool, Rapid Arterial Occlusion Evaluation, Los Angeles Motor Scale, or Field Assessment Stroke Triage for Emergency Destination should be used. “Further research is needed to establish the most effective prehospital stroke severity triage scale,” the authors noted. In all cases, EMS should notify hospitals that a stroke patient is en route.
“When there are several intravenous alteplase–capable hospitals in a well-defined geographic region, extra transportation times to reach a facility capable of endovascular thrombectomy should be limited to no more than 15 minutes in patients with a prehospital stroke severity score suggestive of LVO,” according to the recommendations. “When several hospital options exist within similar travel times, EMS should seek care at the facility capable of offering the highest level of stroke care. Further research is needed to establish travel time parameters for hospital bypass in cases of prehospital suspicion of LVO.”
Outcomes and discharge
Centers should track various treatment and patient outcomes, and all patients discharged to their homes should have appropriate follow-up with specialized stroke services and primary care and be screened for postacute complications.
Government institutions should standardize the organization of stroke care, ensure that stroke patients receive timely care at appropriate hospitals, and facilitate access to secondary prevention and rehabilitation resources after stroke, the authors wrote.
“Programs geared at further improving the knowledge of the public, encouraging primordial and primary prevention, advancing and facilitating acute therapy, improving secondary prevention and recovery from stroke, and reducing disparities in stroke care should be actively developed in a coordinated and collaborative fashion by providers and policymakers at the local, state, and national levels,” the authors concluded. “Such efforts will continue to mitigate the effects of stroke on society.”
Dr. Adeoye had no disclosures. Some coauthors reported research grants and consultant or advisory board positions.
SOURCE: Adeoye O et al. Stroke. 2019 May 20. doi: 10.1161/STR.0000000000000173.
Stroke centers need to collaborate within their regions to assure best practices and optimal access to comprehensive stroke centers as well as newly-designated thrombectomy-capable stroke centers, according to an updated policy statement from the American Stroke Association published in Stroke.
Opeolu Adeoye, MD, associate professor of emergency medicine and neurosurgery at the University of Cincinnati – and chair of the policy statement writing group – and coauthors updated the ASA’s 2005 recommendations for policy makers and public health care agencies to reflect current evidence, the increased availability of endovascular therapy, and new stroke center certifications.
“We have seen monumental advancements in acute stroke care over the past 14 years, and our concept of a comprehensive stroke system of care has evolved as a result,” Dr. Adeoye said in a news release.
While a recommendation to support the initiation of stroke prevention regimens remains unchanged from the 2005 recommendations, the 2019 update emphasizes a need to support long-term adherence to such regimens. To that end, researchers should examine the potential benefits of stroke prevention efforts that incorporate social media, gamification, and other technologies and principles to promote healthy behavior, the authors suggested. Furthermore, technology may allow for the passive surveillance of baseline behaviors and enable researchers to track changes in behavior over time.
Thrombectomy-capable centers
Thrombectomy-capable stroke centers, which have capabilities between those of primary stroke centers and comprehensive stroke centers, provide a relatively new level of acute stroke care. In communities that do not otherwise have access to thrombectomy, these centers play a clear role. In communities with comprehensive stroke centers, their role “is more controversial, and routing plans for patients with a suspected LVO [large vessel occlusion] should always seek the center of highest capability when travel time differences are short,” the statement says.
Timely parenchymal and arterial imaging via CT or MRI are needed to identify the subset of patients who may benefit from thrombectomy. All centers managing stroke patients should develop a plan for the definitive identification and treatment of these patients. Imaging techniques that assess penumbral patterns to identify candidates for endovascular therapy between 6 and 24 hours after patients were last known to be normal “merit broader adoption,” the statement says.
Hospitals without thrombectomy capability should have transfer protocols to allow the rapid treatment of these patients to hospitals with the appropriate level of care. In rural facilities that lack 24/7 imaging and radiology capabilities, this may mean rapid transfer of patients with clinically suspected LVO to hospitals where their work-up may be expedited.
To improve process, centers providing thrombectomy should rigorously track patient flow at all time points from presentation to imaging to intervention. Reperfusion rates, procedural complications, and patient clinical outcomes must be tracked and reported.
Travel times
Triage paradigms and protocols should be developed to ensure that emergency medical service (EMS) providers are able to rapidly identify all patients with a known or suspected stroke and to assess them with a validated and standardized instrument for stroke screening such as FAST (Face, Arm, Speech, Time), Los Angeles Prehospital Stroke Screen, or Cincinnati Prehospital Stroke Scale.
In prehospital patients who screen positive for suspected stroke, a standard prehospital stroke severity assessment tool such as the Cincinnati Stroke Triage Assessment Tool, Rapid Arterial Occlusion Evaluation, Los Angeles Motor Scale, or Field Assessment Stroke Triage for Emergency Destination should be used. “Further research is needed to establish the most effective prehospital stroke severity triage scale,” the authors noted. In all cases, EMS should notify hospitals that a stroke patient is en route.
“When there are several intravenous alteplase–capable hospitals in a well-defined geographic region, extra transportation times to reach a facility capable of endovascular thrombectomy should be limited to no more than 15 minutes in patients with a prehospital stroke severity score suggestive of LVO,” according to the recommendations. “When several hospital options exist within similar travel times, EMS should seek care at the facility capable of offering the highest level of stroke care. Further research is needed to establish travel time parameters for hospital bypass in cases of prehospital suspicion of LVO.”
Outcomes and discharge
Centers should track various treatment and patient outcomes, and all patients discharged to their homes should have appropriate follow-up with specialized stroke services and primary care and be screened for postacute complications.
Government institutions should standardize the organization of stroke care, ensure that stroke patients receive timely care at appropriate hospitals, and facilitate access to secondary prevention and rehabilitation resources after stroke, the authors wrote.
“Programs geared at further improving the knowledge of the public, encouraging primordial and primary prevention, advancing and facilitating acute therapy, improving secondary prevention and recovery from stroke, and reducing disparities in stroke care should be actively developed in a coordinated and collaborative fashion by providers and policymakers at the local, state, and national levels,” the authors concluded. “Such efforts will continue to mitigate the effects of stroke on society.”
Dr. Adeoye had no disclosures. Some coauthors reported research grants and consultant or advisory board positions.
SOURCE: Adeoye O et al. Stroke. 2019 May 20. doi: 10.1161/STR.0000000000000173.
FROM STROKE
New JIA, JIA-associated uveitis guidelines address knowledge gaps
while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.
The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.
“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.
These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”
“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”
As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.
Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.
Recommendations on JIA with associated uveitis
The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.
“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.
Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.
They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.
“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.
“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.
These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.
“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.
Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.
SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .
while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.
The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.
“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.
These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”
“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”
As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.
Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.
Recommendations on JIA with associated uveitis
The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.
“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.
Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.
They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.
“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.
“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.
These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.
“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.
Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.
SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .
while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.
The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.
“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.
These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”
“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”
As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.
Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.
Recommendations on JIA with associated uveitis
The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.
“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.
Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.
They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.
“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.
“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.
These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.
“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.
Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.
SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .
FROM ARTHRITIS CARE & RESEARCH
ACOG guidance addresses cardiac contributors to maternal mortality
NASHVILLE, TENN. – according to new comprehensive guidance from the American College of Obstetricians and Gynecologists.
The toolkit algorithm is called the California Improving Health Care Response to Cardiovascular Disease in Pregnancy and Postpartum Toolkit. It was developed by the Cardiovascular Disease in Pregnancy Postpartum Task Force to serve as a resource for obstetrics, primary care and emergency medicine providers who provide prenatal care or interact with women during the postpartum period. It incldues an overview of clinical assessment and comprehensive management strategies for cardiovascular disease based on risk factors and presenting symptoms.
The guidance also calls for all pregnant and postpartum women with known or suspected CVD to undergo further evaluation by a “Pregnancy Heart Team that includes a cardiologist and maternal–fetal medicine subspecialist, or both, and other subspecialists as necessary.” The guidance was issued in Practice Bulletin 212, Pregnancy and Heart Disease, which is published in the May edition of Obstetrics & Gynecology (Obstet Gynecol. 2019 May;133[5]:e320-e356).
In all, 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period are included in the guidance.
ACOG president Lisa Hollier, MD, convened the task force that developed this guidance to address cardiac contributors to maternal mortality, she said during a press briefing at the ACOG annual clinical and scientific meeting.
“When I began my presidency a year ago, my goal was to bring together a multidisciplinary group of clinicians ... to create clinical guidance that would make a difference in the lives of women," said Dr. Hollier, who is also a professor of obstetrics and gynecology at Baylor College of Medicine, Houston. 
Part of her presidential initiative was centered on eliminating preventable maternal death, and this guidance has the potential to make strides toward that goal, she said. When it comes to CVD in pregnancy, “there is so much we can do to prevent negative outcomes and ensure that moms go home with their babies and are around to see them grow up,” she noted.
CVD is the leading cause of death in pregnant women and women in the postpartum period, accounting for 26.5% of U.S. pregnancy-related deaths.
“It’s critical that we as physicians and health care professionals develop expertise in recognizing the signs and symptoms so that we can save women’s lives,” she said in the press breifing. Dr. Hollier also implored her colleagues to “start using this guidance immediately and prevent more women from dying from cardiovascular complications of pregnancy.”
In this video interview, Dr. Hollier further explains the need for the guidance and its potential for improving maternal mortality rates.
Dr. Hollier reported having no relevant disclosures.
SOURCE: Hollier L et al., Obstet Gynecol. 2019 May;133[5]:e320-56.
NASHVILLE, TENN. – according to new comprehensive guidance from the American College of Obstetricians and Gynecologists.
The toolkit algorithm is called the California Improving Health Care Response to Cardiovascular Disease in Pregnancy and Postpartum Toolkit. It was developed by the Cardiovascular Disease in Pregnancy Postpartum Task Force to serve as a resource for obstetrics, primary care and emergency medicine providers who provide prenatal care or interact with women during the postpartum period. It incldues an overview of clinical assessment and comprehensive management strategies for cardiovascular disease based on risk factors and presenting symptoms.
The guidance also calls for all pregnant and postpartum women with known or suspected CVD to undergo further evaluation by a “Pregnancy Heart Team that includes a cardiologist and maternal–fetal medicine subspecialist, or both, and other subspecialists as necessary.” The guidance was issued in Practice Bulletin 212, Pregnancy and Heart Disease, which is published in the May edition of Obstetrics & Gynecology (Obstet Gynecol. 2019 May;133[5]:e320-e356).
In all, 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period are included in the guidance.
ACOG president Lisa Hollier, MD, convened the task force that developed this guidance to address cardiac contributors to maternal mortality, she said during a press briefing at the ACOG annual clinical and scientific meeting.
“When I began my presidency a year ago, my goal was to bring together a multidisciplinary group of clinicians ... to create clinical guidance that would make a difference in the lives of women," said Dr. Hollier, who is also a professor of obstetrics and gynecology at Baylor College of Medicine, Houston.
Part of her presidential initiative was centered on eliminating preventable maternal death, and this guidance has the potential to make strides toward that goal, she said. When it comes to CVD in pregnancy, “there is so much we can do to prevent negative outcomes and ensure that moms go home with their babies and are around to see them grow up,” she noted.
CVD is the leading cause of death in pregnant women and women in the postpartum period, accounting for 26.5% of U.S. pregnancy-related deaths.
“It’s critical that we as physicians and health care professionals develop expertise in recognizing the signs and symptoms so that we can save women’s lives,” she said in the press breifing. Dr. Hollier also implored her colleagues to “start using this guidance immediately and prevent more women from dying from cardiovascular complications of pregnancy.”
In this video interview, Dr. Hollier further explains the need for the guidance and its potential for improving maternal mortality rates.
Dr. Hollier reported having no relevant disclosures.
SOURCE: Hollier L et al., Obstet Gynecol. 2019 May;133[5]:e320-56.
NASHVILLE, TENN. – according to new comprehensive guidance from the American College of Obstetricians and Gynecologists.
The toolkit algorithm is called the California Improving Health Care Response to Cardiovascular Disease in Pregnancy and Postpartum Toolkit. It was developed by the Cardiovascular Disease in Pregnancy Postpartum Task Force to serve as a resource for obstetrics, primary care and emergency medicine providers who provide prenatal care or interact with women during the postpartum period. It incldues an overview of clinical assessment and comprehensive management strategies for cardiovascular disease based on risk factors and presenting symptoms.
The guidance also calls for all pregnant and postpartum women with known or suspected CVD to undergo further evaluation by a “Pregnancy Heart Team that includes a cardiologist and maternal–fetal medicine subspecialist, or both, and other subspecialists as necessary.” The guidance was issued in Practice Bulletin 212, Pregnancy and Heart Disease, which is published in the May edition of Obstetrics & Gynecology (Obstet Gynecol. 2019 May;133[5]:e320-e356).
In all, 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period are included in the guidance.
ACOG president Lisa Hollier, MD, convened the task force that developed this guidance to address cardiac contributors to maternal mortality, she said during a press briefing at the ACOG annual clinical and scientific meeting.
“When I began my presidency a year ago, my goal was to bring together a multidisciplinary group of clinicians ... to create clinical guidance that would make a difference in the lives of women," said Dr. Hollier, who is also a professor of obstetrics and gynecology at Baylor College of Medicine, Houston.
Part of her presidential initiative was centered on eliminating preventable maternal death, and this guidance has the potential to make strides toward that goal, she said. When it comes to CVD in pregnancy, “there is so much we can do to prevent negative outcomes and ensure that moms go home with their babies and are around to see them grow up,” she noted.
CVD is the leading cause of death in pregnant women and women in the postpartum period, accounting for 26.5% of U.S. pregnancy-related deaths.
“It’s critical that we as physicians and health care professionals develop expertise in recognizing the signs and symptoms so that we can save women’s lives,” she said in the press breifing. Dr. Hollier also implored her colleagues to “start using this guidance immediately and prevent more women from dying from cardiovascular complications of pregnancy.”
In this video interview, Dr. Hollier further explains the need for the guidance and its potential for improving maternal mortality rates.
Dr. Hollier reported having no relevant disclosures.
SOURCE: Hollier L et al., Obstet Gynecol. 2019 May;133[5]:e320-56.
REPORTING FROM ACOG 2019
Experts propose new definition and recommendations for Alzheimer’s-like disorder
An international group of experts has proposed a new name, staging criteria, and recommendations for a recently recognized brain disorder that mimics Alzheimer’s disease and is marked by a proteinopathy caused by malformed transactive response DNA-binding protein of 43 kDa (TDP-43).
The term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in an effort to raise awareness and kick-start research into this “pathway to dementia,” the experts wrote in a report appearing in Brain.
“As there is currently no universally agreed-upon terminology or staging system for common age-related TDP-43 proteinopathy, this condition is understudied and not well recognized, even among investigators in the field of dementia research,” wrote the authors of the report, led by Peter T. Nelson, MD, PhD, of the University of Kentucky, Lexington.
LATE neuropathologic changes, associated with a progressive amnesia syndrome that mimics Alzheimer’s, are seen in more than 20% of individuals past the age of 80 years, according to large, community-based autopsy series. It coexists with Alzheimer’s disease in many patients, lowering the threshold for developing dementia, authors said.
The term LATE is designed to encompass several other terms related to TDP-43 pathology, including hippocampal sclerosis and cerebral age-related TDP-43 with sclerosis, Dr. Nelson and coauthors noted in their report.
The TDP-43 protein is encoded by the TARDBP gene and provides several functions related to the regulation of gene expression, the authors wrote.
Misfolded TDP-43 was known to play a causative role in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, the authors noted, and then was also identified in the brains of older individuals with hippocampal sclerosis or Alzheimer’s disease neuropathologic changes.
The authors proposed a three-stage classification system for LATE neuropathologic change based on TDP-43 immunohistochemistry performed during routine autopsy evaluation of the amygdala, hippocampus, and middle frontal gyrus.
The amygdala is an area affected early in the course of the disease (Stage 1), whereas involvement of the hippocampus represents a more intermediate stage (Stage 2), and the middle frontal gyrus is more affected in advanced stages of the disease (Stage 3), according to the schema.
Five genes have been identified with risk alleles for LATE neuropathologic changes, authors said. Of note, several groups have found that the apolipoprotein E epsilon 4 (APOE4) allele, known to be a risk factor for Alzheimer’s disease neuropathologic changes and Lewy body disease, is also linked to increased risk of TDP-43 proteinopathy.
There are no established biomarkers specific to TDP-43 proteinopathy yet, which hampers development of clinical trials designed to test interventions to treat or prevent LATE, Dr. Nelson and colleagues said in their report.
LATE could also obscure the effects of potentially disease-modifying agents being tested in Alzheimer’s disease clinical trials, which can complicate the interpretation of study results, they added.
“Until there are biomarkers for LATE, clinical trials should be powered to account for TDP-43 proteinopathy,” they wrote.
Dr. Nelson and coauthors of the report in Brain reported no competing interests.
SOURCE: Nelson PT, et al. Brain. 2019 Apr 30. doi: 10.1093/brain/awz099
Alois Alzheimer’s original patient was 51 years old, and for roughly 70 years Alzheimer’s disease was considered a rare disease that caused presenile dementia. In the 1970s, Robert Katzman, MD, and Robert D. Terry, MD, equated the neuropathologic features of Alzheimer’s disease with the more common senile dementia, and since then we have recognized Alzheimer’s disease as the most common form of dementia. Autopsy studies of patients dying in their 80s and 90s, however, has revealed that far more common than pure Alzheimer’s disease is a mixed neuropathologic picture. In addition, with the advent of biomarker studies a substantial number of individuals have “suspected non-Alzheimer pathology.”
Interestingly, the authors identify the apolipoprotein E epsilon 4 (APOE4) allele as a predisposing factor for LATE, although given the advanced age of the LATE patient population, one could argue that a certain degree of resilience extended their lives into the LATE age range.
In contrast, in the Alzheimer’s Disease Sequencing Project, among those with autopsy confirmation, the prevalence of APOE4 in Braak stage 5-6 declines with succeeding decades so that, by the 80s and 90s, the prevalence of APOE2 is actually higher at 7.3% vs. 4.1% with APOE4 for ages 80 to younger than 85 years, 9.3% with APOE2 vs. 8.6% with APOE4 for 85 to younger than 90 years, and 16.7% with APOE2 vs. 6.9% with APOE4 for ages 90 years and above.
Our understanding of age-related cognitive decline, from the normal to the pathological ends of the spectrum, continues to evolve, and LATE is simply the latest addition to our growing knowledge base that will further inform clinical diagnosis, research, and experimental therapeutics.
Richard J. Caselli, MD, is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.
Alois Alzheimer’s original patient was 51 years old, and for roughly 70 years Alzheimer’s disease was considered a rare disease that caused presenile dementia. In the 1970s, Robert Katzman, MD, and Robert D. Terry, MD, equated the neuropathologic features of Alzheimer’s disease with the more common senile dementia, and since then we have recognized Alzheimer’s disease as the most common form of dementia. Autopsy studies of patients dying in their 80s and 90s, however, has revealed that far more common than pure Alzheimer’s disease is a mixed neuropathologic picture. In addition, with the advent of biomarker studies a substantial number of individuals have “suspected non-Alzheimer pathology.”
Interestingly, the authors identify the apolipoprotein E epsilon 4 (APOE4) allele as a predisposing factor for LATE, although given the advanced age of the LATE patient population, one could argue that a certain degree of resilience extended their lives into the LATE age range.
In contrast, in the Alzheimer’s Disease Sequencing Project, among those with autopsy confirmation, the prevalence of APOE4 in Braak stage 5-6 declines with succeeding decades so that, by the 80s and 90s, the prevalence of APOE2 is actually higher at 7.3% vs. 4.1% with APOE4 for ages 80 to younger than 85 years, 9.3% with APOE2 vs. 8.6% with APOE4 for 85 to younger than 90 years, and 16.7% with APOE2 vs. 6.9% with APOE4 for ages 90 years and above.
Our understanding of age-related cognitive decline, from the normal to the pathological ends of the spectrum, continues to evolve, and LATE is simply the latest addition to our growing knowledge base that will further inform clinical diagnosis, research, and experimental therapeutics.
Richard J. Caselli, MD, is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.
Alois Alzheimer’s original patient was 51 years old, and for roughly 70 years Alzheimer’s disease was considered a rare disease that caused presenile dementia. In the 1970s, Robert Katzman, MD, and Robert D. Terry, MD, equated the neuropathologic features of Alzheimer’s disease with the more common senile dementia, and since then we have recognized Alzheimer’s disease as the most common form of dementia. Autopsy studies of patients dying in their 80s and 90s, however, has revealed that far more common than pure Alzheimer’s disease is a mixed neuropathologic picture. In addition, with the advent of biomarker studies a substantial number of individuals have “suspected non-Alzheimer pathology.”
Interestingly, the authors identify the apolipoprotein E epsilon 4 (APOE4) allele as a predisposing factor for LATE, although given the advanced age of the LATE patient population, one could argue that a certain degree of resilience extended their lives into the LATE age range.
In contrast, in the Alzheimer’s Disease Sequencing Project, among those with autopsy confirmation, the prevalence of APOE4 in Braak stage 5-6 declines with succeeding decades so that, by the 80s and 90s, the prevalence of APOE2 is actually higher at 7.3% vs. 4.1% with APOE4 for ages 80 to younger than 85 years, 9.3% with APOE2 vs. 8.6% with APOE4 for 85 to younger than 90 years, and 16.7% with APOE2 vs. 6.9% with APOE4 for ages 90 years and above.
Our understanding of age-related cognitive decline, from the normal to the pathological ends of the spectrum, continues to evolve, and LATE is simply the latest addition to our growing knowledge base that will further inform clinical diagnosis, research, and experimental therapeutics.
Richard J. Caselli, MD, is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.
An international group of experts has proposed a new name, staging criteria, and recommendations for a recently recognized brain disorder that mimics Alzheimer’s disease and is marked by a proteinopathy caused by malformed transactive response DNA-binding protein of 43 kDa (TDP-43).
The term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in an effort to raise awareness and kick-start research into this “pathway to dementia,” the experts wrote in a report appearing in Brain.
“As there is currently no universally agreed-upon terminology or staging system for common age-related TDP-43 proteinopathy, this condition is understudied and not well recognized, even among investigators in the field of dementia research,” wrote the authors of the report, led by Peter T. Nelson, MD, PhD, of the University of Kentucky, Lexington.
LATE neuropathologic changes, associated with a progressive amnesia syndrome that mimics Alzheimer’s, are seen in more than 20% of individuals past the age of 80 years, according to large, community-based autopsy series. It coexists with Alzheimer’s disease in many patients, lowering the threshold for developing dementia, authors said.
The term LATE is designed to encompass several other terms related to TDP-43 pathology, including hippocampal sclerosis and cerebral age-related TDP-43 with sclerosis, Dr. Nelson and coauthors noted in their report.
The TDP-43 protein is encoded by the TARDBP gene and provides several functions related to the regulation of gene expression, the authors wrote.
Misfolded TDP-43 was known to play a causative role in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, the authors noted, and then was also identified in the brains of older individuals with hippocampal sclerosis or Alzheimer’s disease neuropathologic changes.
The authors proposed a three-stage classification system for LATE neuropathologic change based on TDP-43 immunohistochemistry performed during routine autopsy evaluation of the amygdala, hippocampus, and middle frontal gyrus.
The amygdala is an area affected early in the course of the disease (Stage 1), whereas involvement of the hippocampus represents a more intermediate stage (Stage 2), and the middle frontal gyrus is more affected in advanced stages of the disease (Stage 3), according to the schema.
Five genes have been identified with risk alleles for LATE neuropathologic changes, authors said. Of note, several groups have found that the apolipoprotein E epsilon 4 (APOE4) allele, known to be a risk factor for Alzheimer’s disease neuropathologic changes and Lewy body disease, is also linked to increased risk of TDP-43 proteinopathy.
There are no established biomarkers specific to TDP-43 proteinopathy yet, which hampers development of clinical trials designed to test interventions to treat or prevent LATE, Dr. Nelson and colleagues said in their report.
LATE could also obscure the effects of potentially disease-modifying agents being tested in Alzheimer’s disease clinical trials, which can complicate the interpretation of study results, they added.
“Until there are biomarkers for LATE, clinical trials should be powered to account for TDP-43 proteinopathy,” they wrote.
Dr. Nelson and coauthors of the report in Brain reported no competing interests.
SOURCE: Nelson PT, et al. Brain. 2019 Apr 30. doi: 10.1093/brain/awz099
An international group of experts has proposed a new name, staging criteria, and recommendations for a recently recognized brain disorder that mimics Alzheimer’s disease and is marked by a proteinopathy caused by malformed transactive response DNA-binding protein of 43 kDa (TDP-43).
The term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in an effort to raise awareness and kick-start research into this “pathway to dementia,” the experts wrote in a report appearing in Brain.
“As there is currently no universally agreed-upon terminology or staging system for common age-related TDP-43 proteinopathy, this condition is understudied and not well recognized, even among investigators in the field of dementia research,” wrote the authors of the report, led by Peter T. Nelson, MD, PhD, of the University of Kentucky, Lexington.
LATE neuropathologic changes, associated with a progressive amnesia syndrome that mimics Alzheimer’s, are seen in more than 20% of individuals past the age of 80 years, according to large, community-based autopsy series. It coexists with Alzheimer’s disease in many patients, lowering the threshold for developing dementia, authors said.
The term LATE is designed to encompass several other terms related to TDP-43 pathology, including hippocampal sclerosis and cerebral age-related TDP-43 with sclerosis, Dr. Nelson and coauthors noted in their report.
The TDP-43 protein is encoded by the TARDBP gene and provides several functions related to the regulation of gene expression, the authors wrote.
Misfolded TDP-43 was known to play a causative role in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, the authors noted, and then was also identified in the brains of older individuals with hippocampal sclerosis or Alzheimer’s disease neuropathologic changes.
The authors proposed a three-stage classification system for LATE neuropathologic change based on TDP-43 immunohistochemistry performed during routine autopsy evaluation of the amygdala, hippocampus, and middle frontal gyrus.
The amygdala is an area affected early in the course of the disease (Stage 1), whereas involvement of the hippocampus represents a more intermediate stage (Stage 2), and the middle frontal gyrus is more affected in advanced stages of the disease (Stage 3), according to the schema.
Five genes have been identified with risk alleles for LATE neuropathologic changes, authors said. Of note, several groups have found that the apolipoprotein E epsilon 4 (APOE4) allele, known to be a risk factor for Alzheimer’s disease neuropathologic changes and Lewy body disease, is also linked to increased risk of TDP-43 proteinopathy.
There are no established biomarkers specific to TDP-43 proteinopathy yet, which hampers development of clinical trials designed to test interventions to treat or prevent LATE, Dr. Nelson and colleagues said in their report.
LATE could also obscure the effects of potentially disease-modifying agents being tested in Alzheimer’s disease clinical trials, which can complicate the interpretation of study results, they added.
“Until there are biomarkers for LATE, clinical trials should be powered to account for TDP-43 proteinopathy,” they wrote.
Dr. Nelson and coauthors of the report in Brain reported no competing interests.
SOURCE: Nelson PT, et al. Brain. 2019 Apr 30. doi: 10.1093/brain/awz099
FROM BRAIN
Are guidelines relevant?
The recent publication of the changes and current levels of evidence for the guidelines from the American College of Cardiology, American Heart Association, and the European Society of Cardiology once again indicates that the level of high-quality scientific data supporting the decision making process is limited.
Of the thousands of recommendations among the guidelines provided, level A data – which is supported by at least two randomized, controlled trials (RCT), arguably the gold standard for the proof of benefit of a treatment program – was available in only 8.5% of ACC/AHA recommendations and in 14.2% of ESC recommendations. The recent review covering guidelines published from 2008 to 2018 has changed very little since the previous review carried out on data collected between 1999 and 2014 (JAMA. 2019 Mar 19;321[11]:1069-80). Admittedly, by the nature of their design, RCTs represent a very special subset of any disease process but they are the best we can do. The remainder of the guidelines is supported by nonrandomized data and consensus opinion of “experts.” The absence of randomized data in the rest of the guidelines creates an area of uncertainty between clinical practice and outcomes.
Guidelines have been with us for almost 30 years and have provided a near “cookbook recipe” for the treatment of almost the totality of cardiovascular care, both in the United States and Europe. There is little evidence that guideline dissemination results in a beneficial effect on cardiovascular care, instead reflecting the contemporary published research and informed opinion of our generation.
Despite the limitation of hard data based on RCTs, cardiovascular mortality has leveled off in the last few years. Although there are a number of areas that could be investigated with more focused and practical RCTs, there has been little enthusiasm by either the National Heart, Lung, and Blood Institute or the pharmaceutical or device industries to investigate existing cardiovascular drugs and/or devices to better elucidate nuanced therapy for subsets of heart disease that remain in the uncertain data areas. In fact, the current report shows that there has been little change in guidelines in the last 10 years. Most effort has been focused on new drug development and application.
Much of the advance in cardiovascular care and decrease in mortality is a result of the development of new drugs for the treatment of hypertension, management of hypercholesterolemia, and MI, together with coronary angiography and its interventional permutations of the previous 50 years. Those advances are now part of our knowledge base, our therapeutic DNA, and in the absence of some new scientific breakthrough, there is little to expect from future guideline development. Medical students and house officers are being taught as fact what we found as exciting new therapy just a few short years ago. Guidelines are now part of textbook knowledge and until new clinical outcome are reported, guidelines will probably serve a useful reference material but will not lead to much change in clinical care.
Even so, treating the patient in the clinic and in the hospital still requires the doctor to practice the “art” of medicine and to synthesize therapy based on the paucity of scientific data and quasi knowledge acquired over a generation.
The appreciation that much is unknown gives the doctor the humility required to be sensitive to patient needs and their symptoms and the aspiration for new, science-based data. This is still part of the excitement of being a doctor.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.
The recent publication of the changes and current levels of evidence for the guidelines from the American College of Cardiology, American Heart Association, and the European Society of Cardiology once again indicates that the level of high-quality scientific data supporting the decision making process is limited.
Of the thousands of recommendations among the guidelines provided, level A data – which is supported by at least two randomized, controlled trials (RCT), arguably the gold standard for the proof of benefit of a treatment program – was available in only 8.5% of ACC/AHA recommendations and in 14.2% of ESC recommendations. The recent review covering guidelines published from 2008 to 2018 has changed very little since the previous review carried out on data collected between 1999 and 2014 (JAMA. 2019 Mar 19;321[11]:1069-80). Admittedly, by the nature of their design, RCTs represent a very special subset of any disease process but they are the best we can do. The remainder of the guidelines is supported by nonrandomized data and consensus opinion of “experts.” The absence of randomized data in the rest of the guidelines creates an area of uncertainty between clinical practice and outcomes.
Guidelines have been with us for almost 30 years and have provided a near “cookbook recipe” for the treatment of almost the totality of cardiovascular care, both in the United States and Europe. There is little evidence that guideline dissemination results in a beneficial effect on cardiovascular care, instead reflecting the contemporary published research and informed opinion of our generation.
Despite the limitation of hard data based on RCTs, cardiovascular mortality has leveled off in the last few years. Although there are a number of areas that could be investigated with more focused and practical RCTs, there has been little enthusiasm by either the National Heart, Lung, and Blood Institute or the pharmaceutical or device industries to investigate existing cardiovascular drugs and/or devices to better elucidate nuanced therapy for subsets of heart disease that remain in the uncertain data areas. In fact, the current report shows that there has been little change in guidelines in the last 10 years. Most effort has been focused on new drug development and application.
Much of the advance in cardiovascular care and decrease in mortality is a result of the development of new drugs for the treatment of hypertension, management of hypercholesterolemia, and MI, together with coronary angiography and its interventional permutations of the previous 50 years. Those advances are now part of our knowledge base, our therapeutic DNA, and in the absence of some new scientific breakthrough, there is little to expect from future guideline development. Medical students and house officers are being taught as fact what we found as exciting new therapy just a few short years ago. Guidelines are now part of textbook knowledge and until new clinical outcome are reported, guidelines will probably serve a useful reference material but will not lead to much change in clinical care.
Even so, treating the patient in the clinic and in the hospital still requires the doctor to practice the “art” of medicine and to synthesize therapy based on the paucity of scientific data and quasi knowledge acquired over a generation.
The appreciation that much is unknown gives the doctor the humility required to be sensitive to patient needs and their symptoms and the aspiration for new, science-based data. This is still part of the excitement of being a doctor.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.
The recent publication of the changes and current levels of evidence for the guidelines from the American College of Cardiology, American Heart Association, and the European Society of Cardiology once again indicates that the level of high-quality scientific data supporting the decision making process is limited.
Of the thousands of recommendations among the guidelines provided, level A data – which is supported by at least two randomized, controlled trials (RCT), arguably the gold standard for the proof of benefit of a treatment program – was available in only 8.5% of ACC/AHA recommendations and in 14.2% of ESC recommendations. The recent review covering guidelines published from 2008 to 2018 has changed very little since the previous review carried out on data collected between 1999 and 2014 (JAMA. 2019 Mar 19;321[11]:1069-80). Admittedly, by the nature of their design, RCTs represent a very special subset of any disease process but they are the best we can do. The remainder of the guidelines is supported by nonrandomized data and consensus opinion of “experts.” The absence of randomized data in the rest of the guidelines creates an area of uncertainty between clinical practice and outcomes.
Guidelines have been with us for almost 30 years and have provided a near “cookbook recipe” for the treatment of almost the totality of cardiovascular care, both in the United States and Europe. There is little evidence that guideline dissemination results in a beneficial effect on cardiovascular care, instead reflecting the contemporary published research and informed opinion of our generation.
Despite the limitation of hard data based on RCTs, cardiovascular mortality has leveled off in the last few years. Although there are a number of areas that could be investigated with more focused and practical RCTs, there has been little enthusiasm by either the National Heart, Lung, and Blood Institute or the pharmaceutical or device industries to investigate existing cardiovascular drugs and/or devices to better elucidate nuanced therapy for subsets of heart disease that remain in the uncertain data areas. In fact, the current report shows that there has been little change in guidelines in the last 10 years. Most effort has been focused on new drug development and application.
Much of the advance in cardiovascular care and decrease in mortality is a result of the development of new drugs for the treatment of hypertension, management of hypercholesterolemia, and MI, together with coronary angiography and its interventional permutations of the previous 50 years. Those advances are now part of our knowledge base, our therapeutic DNA, and in the absence of some new scientific breakthrough, there is little to expect from future guideline development. Medical students and house officers are being taught as fact what we found as exciting new therapy just a few short years ago. Guidelines are now part of textbook knowledge and until new clinical outcome are reported, guidelines will probably serve a useful reference material but will not lead to much change in clinical care.
Even so, treating the patient in the clinic and in the hospital still requires the doctor to practice the “art” of medicine and to synthesize therapy based on the paucity of scientific data and quasi knowledge acquired over a generation.
The appreciation that much is unknown gives the doctor the humility required to be sensitive to patient needs and their symptoms and the aspiration for new, science-based data. This is still part of the excitement of being a doctor.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.
New consensus recommendations on vaccination in hemophilia
New consensus statements, released by a panel of 11 experts, provide 27 specific recommendations related to the use of vaccines in patients with hemophilia.
The recommendations from the Italian Haemophilia and Vaccinations (HEVA) project were authored by an 11-member committee with expertise in both hemophilia and immunization. The authors reviewed 20 relevant studies published before August 30, 2017.
“Vaccination of patients with severe congenital bleeding disorders remains a challenge, and clinicians are often uncertain about immunization recommendations for these patients,” wrote Elena Santagostino, MD, PhD, of the Centro Emofilia e Trombosi Angelo Bianchi Bonomi in Milan, Italy, and her colleagues. The report is published in Haemophilia.
The statements were also validated by separate groups of clinicians at hemophilia treatment centers across Italy.
The key issues described included vaccination schedule, route of administration, vaccination of patients with antibodies that impede coagulation factor VIII inhibitors, and risk of inhibitor formation with vaccination.
In general, committee members agreed on the majority of statements, with the exception of those related to the possible links between vaccination and inhibitor formation. There were a total of five statements on which no consensus was reached.
Vaccinations in both adults and children with hemophilia should be provided in accordance with the institutional schedule for those without bleeding disorders, according to the recommendations.
“The only difference is that vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk,” the experts wrote.
The panel also reported that current data suggest that vaccination timing is not affected by the timing of factor VIII replacement.
The authors acknowledged that the recommendations were formed by a group of experts from Italy using a specific consensus framework. As a result, they may not be applicable to all patient populations.
The manuscript was supported by Sobi. The authors reported financial relationships with Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, and other companies.
SOURCE: Santagostino E et al. Haemophilia. 2019 Apr 16. doi: 10.1111/hae.13756.
New consensus statements, released by a panel of 11 experts, provide 27 specific recommendations related to the use of vaccines in patients with hemophilia.
The recommendations from the Italian Haemophilia and Vaccinations (HEVA) project were authored by an 11-member committee with expertise in both hemophilia and immunization. The authors reviewed 20 relevant studies published before August 30, 2017.
“Vaccination of patients with severe congenital bleeding disorders remains a challenge, and clinicians are often uncertain about immunization recommendations for these patients,” wrote Elena Santagostino, MD, PhD, of the Centro Emofilia e Trombosi Angelo Bianchi Bonomi in Milan, Italy, and her colleagues. The report is published in Haemophilia.
The statements were also validated by separate groups of clinicians at hemophilia treatment centers across Italy.
The key issues described included vaccination schedule, route of administration, vaccination of patients with antibodies that impede coagulation factor VIII inhibitors, and risk of inhibitor formation with vaccination.
In general, committee members agreed on the majority of statements, with the exception of those related to the possible links between vaccination and inhibitor formation. There were a total of five statements on which no consensus was reached.
Vaccinations in both adults and children with hemophilia should be provided in accordance with the institutional schedule for those without bleeding disorders, according to the recommendations.
“The only difference is that vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk,” the experts wrote.
The panel also reported that current data suggest that vaccination timing is not affected by the timing of factor VIII replacement.
The authors acknowledged that the recommendations were formed by a group of experts from Italy using a specific consensus framework. As a result, they may not be applicable to all patient populations.
The manuscript was supported by Sobi. The authors reported financial relationships with Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, and other companies.
SOURCE: Santagostino E et al. Haemophilia. 2019 Apr 16. doi: 10.1111/hae.13756.
New consensus statements, released by a panel of 11 experts, provide 27 specific recommendations related to the use of vaccines in patients with hemophilia.
The recommendations from the Italian Haemophilia and Vaccinations (HEVA) project were authored by an 11-member committee with expertise in both hemophilia and immunization. The authors reviewed 20 relevant studies published before August 30, 2017.
“Vaccination of patients with severe congenital bleeding disorders remains a challenge, and clinicians are often uncertain about immunization recommendations for these patients,” wrote Elena Santagostino, MD, PhD, of the Centro Emofilia e Trombosi Angelo Bianchi Bonomi in Milan, Italy, and her colleagues. The report is published in Haemophilia.
The statements were also validated by separate groups of clinicians at hemophilia treatment centers across Italy.
The key issues described included vaccination schedule, route of administration, vaccination of patients with antibodies that impede coagulation factor VIII inhibitors, and risk of inhibitor formation with vaccination.
In general, committee members agreed on the majority of statements, with the exception of those related to the possible links between vaccination and inhibitor formation. There were a total of five statements on which no consensus was reached.
Vaccinations in both adults and children with hemophilia should be provided in accordance with the institutional schedule for those without bleeding disorders, according to the recommendations.
“The only difference is that vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk,” the experts wrote.
The panel also reported that current data suggest that vaccination timing is not affected by the timing of factor VIII replacement.
The authors acknowledged that the recommendations were formed by a group of experts from Italy using a specific consensus framework. As a result, they may not be applicable to all patient populations.
The manuscript was supported by Sobi. The authors reported financial relationships with Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, and other companies.
SOURCE: Santagostino E et al. Haemophilia. 2019 Apr 16. doi: 10.1111/hae.13756.
FROM HAEMOPHILIA
First North American clinical guidelines for hidradenitis suppurativa released
Rigorous evidence is unavailable for most interventions for treating hidradenitis suppurativa (HS), so management needs to be individualized, according to the
The guidelines were published in the Journal of the American Academy of Dermatology.
In an interview, Christopher Sayed, MD, cochair of the guidelines committee, of the department of dermatology at the University of North Carolina, Chapel Hill, said in an interview that the North American guidelines vary from the British Association of Dermatologists (Br J Dermatol. 2018 Dec 15. doi: 10.1111/bjd.17537) and European guidelines (J Eur Acad Dermatol Venereol. 2015 Apr;29[4]:619-44). For example, surgery is an active treatment option for various stages of the disorder in the North American guidelines, whereas surgery is considered a last-ditch effort in the British and European guidelines.
Surgical intervention is often needed “for patients to be the best they can be, and it can be difficult for medicine alone to fix [certain] patients,” Dr. Sayed said. This point that “using medical treatment alone or just surgical treatment alone often doesn’t lead to the best outcome” is stressed in the North American guidelines, he noted.
Limited evidence for high-level recommendations
Adalimumab (Humira), a tumor necrosis factor blocker, was the only therapy for which level 1A evidence is available, and this is because of its study in large-scale randomized controlled trials. (The Food and Drug Administration approved adalimumab in 2015 for treating moderate to severe HS.) Other biologic therapies such as infliximab, anakinra, and ustekinumab carry level 2B recommendations, which Dr. Sayed said will likely influence the availability of these therapies.
Similarly, Nd:YAG laser carries a level 2B recommendation, as does wide excision surgical intervention.
Many of the other treatment modalities explored in the guidelines are not well supported by the literature, according to Dr. Sayed . “The vast majority ... had category C recommendations,” he said. “Some things we tried to evaluate that, really, we can’t give any recommendation on at all because there was no evidence.” He noted that changes in lifestyle and dietary practices are issues patients with HS frequently bring up, but they carry very little evidence of benefit in the literature.
“Even things we use very commonly in HS are often supported by weak evidence because we have to rely on clinical experience. ... There’s just not funding for trials of older drugs or lifestyle interventions,” he said. Treatment mainstays such as tetracycline-class antibiotics, for example, similarly have no large-scale randomized controlled trials to support their use.
Consider comorbidity screening
Treatment is frequently complicated by patient comorbidities, including type 2 diabetes, metabolic syndrome, polycystic ovary syndrome (PCOS), and impaired sexual health, said Dr. Sayed.
“The disease leads to scarring and disfigurement, and can [have a] higher impact on quality of life than almost any other dermatologic disease if you compare them side by side using quality of life measures,” he noted. “We know these patients are more likely to have depression, there are high rates of suicide among these patients. A lot of that has to do with the fact that it’s a chronic disease where there is pain and disfigurement, and patients often grow very, very frustrated in part due to the disease.”
He advised consistent follow-up to ensure patients are not frustrated because of lack of perceived progress.
No one-size-fits-all approach
Dr. Sayed said individualized management is one of the most important parts of taking care of a patient with HS. For example, patients with Hurley stage 1 and Hurley stage 2 variations of the disease may present very differently, and that is the reason why the guidelines do not offer a stepwise treatment algorithm for the disease.
“[The guidelines] have many treatments that may overlap different stages of disease, where those things might need to be used together,” he said. “It takes a lot of discussion with patients about their treatment preferences and listening to whether their disease is progressing or not, whether or not it’s stable, and then trying to figure out whether things like surgery fit into the treatment strategy.”
Despite these recommendations, there may be situations where the answer is not listed in the guidelines. “The guidelines are based on evidence that’s available at the time we review the literature,” he said. “For many patients, they may fail every treatment that’s recommended within the guidelines. There will be times where you have to be creative for patients and go beyond what the guidelines can currently recommend and give patients the treatment that they need even when it seems like all options have been exhausted.”
The authors report relationships with 3M, AbbVie, Adelphi Values, Amgen, BSN, Celgene, Chemocentryx, Coloplast, Galderma, Hidramed Solutions, Hollister, the HS Foundation, Incyte, InflaRx, Integra, Janssen, KCI Inc., Lenicura, Leo, Lilly, The Microdermis Corporation, Novartis, Pfizer, UCB, Valeant, and XBiotech both inside and outside the supported work.
SOURCES: Alikhan A et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.067; Alikhan A et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.068.
Rigorous evidence is unavailable for most interventions for treating hidradenitis suppurativa (HS), so management needs to be individualized, according to the
The guidelines were published in the Journal of the American Academy of Dermatology.
In an interview, Christopher Sayed, MD, cochair of the guidelines committee, of the department of dermatology at the University of North Carolina, Chapel Hill, said in an interview that the North American guidelines vary from the British Association of Dermatologists (Br J Dermatol. 2018 Dec 15. doi: 10.1111/bjd.17537) and European guidelines (J Eur Acad Dermatol Venereol. 2015 Apr;29[4]:619-44). For example, surgery is an active treatment option for various stages of the disorder in the North American guidelines, whereas surgery is considered a last-ditch effort in the British and European guidelines.
Surgical intervention is often needed “for patients to be the best they can be, and it can be difficult for medicine alone to fix [certain] patients,” Dr. Sayed said. This point that “using medical treatment alone or just surgical treatment alone often doesn’t lead to the best outcome” is stressed in the North American guidelines, he noted.
Limited evidence for high-level recommendations
Adalimumab (Humira), a tumor necrosis factor blocker, was the only therapy for which level 1A evidence is available, and this is because of its study in large-scale randomized controlled trials. (The Food and Drug Administration approved adalimumab in 2015 for treating moderate to severe HS.) Other biologic therapies such as infliximab, anakinra, and ustekinumab carry level 2B recommendations, which Dr. Sayed said will likely influence the availability of these therapies.
Similarly, Nd:YAG laser carries a level 2B recommendation, as does wide excision surgical intervention.
Many of the other treatment modalities explored in the guidelines are not well supported by the literature, according to Dr. Sayed . “The vast majority ... had category C recommendations,” he said. “Some things we tried to evaluate that, really, we can’t give any recommendation on at all because there was no evidence.” He noted that changes in lifestyle and dietary practices are issues patients with HS frequently bring up, but they carry very little evidence of benefit in the literature.
“Even things we use very commonly in HS are often supported by weak evidence because we have to rely on clinical experience. ... There’s just not funding for trials of older drugs or lifestyle interventions,” he said. Treatment mainstays such as tetracycline-class antibiotics, for example, similarly have no large-scale randomized controlled trials to support their use.
Consider comorbidity screening
Treatment is frequently complicated by patient comorbidities, including type 2 diabetes, metabolic syndrome, polycystic ovary syndrome (PCOS), and impaired sexual health, said Dr. Sayed.
“The disease leads to scarring and disfigurement, and can [have a] higher impact on quality of life than almost any other dermatologic disease if you compare them side by side using quality of life measures,” he noted. “We know these patients are more likely to have depression, there are high rates of suicide among these patients. A lot of that has to do with the fact that it’s a chronic disease where there is pain and disfigurement, and patients often grow very, very frustrated in part due to the disease.”
He advised consistent follow-up to ensure patients are not frustrated because of lack of perceived progress.
No one-size-fits-all approach
Dr. Sayed said individualized management is one of the most important parts of taking care of a patient with HS. For example, patients with Hurley stage 1 and Hurley stage 2 variations of the disease may present very differently, and that is the reason why the guidelines do not offer a stepwise treatment algorithm for the disease.
“[The guidelines] have many treatments that may overlap different stages of disease, where those things might need to be used together,” he said. “It takes a lot of discussion with patients about their treatment preferences and listening to whether their disease is progressing or not, whether or not it’s stable, and then trying to figure out whether things like surgery fit into the treatment strategy.”
Despite these recommendations, there may be situations where the answer is not listed in the guidelines. “The guidelines are based on evidence that’s available at the time we review the literature,” he said. “For many patients, they may fail every treatment that’s recommended within the guidelines. There will be times where you have to be creative for patients and go beyond what the guidelines can currently recommend and give patients the treatment that they need even when it seems like all options have been exhausted.”
The authors report relationships with 3M, AbbVie, Adelphi Values, Amgen, BSN, Celgene, Chemocentryx, Coloplast, Galderma, Hidramed Solutions, Hollister, the HS Foundation, Incyte, InflaRx, Integra, Janssen, KCI Inc., Lenicura, Leo, Lilly, The Microdermis Corporation, Novartis, Pfizer, UCB, Valeant, and XBiotech both inside and outside the supported work.
SOURCES: Alikhan A et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.067; Alikhan A et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.068.
Rigorous evidence is unavailable for most interventions for treating hidradenitis suppurativa (HS), so management needs to be individualized, according to the
The guidelines were published in the Journal of the American Academy of Dermatology.
In an interview, Christopher Sayed, MD, cochair of the guidelines committee, of the department of dermatology at the University of North Carolina, Chapel Hill, said in an interview that the North American guidelines vary from the British Association of Dermatologists (Br J Dermatol. 2018 Dec 15. doi: 10.1111/bjd.17537) and European guidelines (J Eur Acad Dermatol Venereol. 2015 Apr;29[4]:619-44). For example, surgery is an active treatment option for various stages of the disorder in the North American guidelines, whereas surgery is considered a last-ditch effort in the British and European guidelines.
Surgical intervention is often needed “for patients to be the best they can be, and it can be difficult for medicine alone to fix [certain] patients,” Dr. Sayed said. This point that “using medical treatment alone or just surgical treatment alone often doesn’t lead to the best outcome” is stressed in the North American guidelines, he noted.
Limited evidence for high-level recommendations
Adalimumab (Humira), a tumor necrosis factor blocker, was the only therapy for which level 1A evidence is available, and this is because of its study in large-scale randomized controlled trials. (The Food and Drug Administration approved adalimumab in 2015 for treating moderate to severe HS.) Other biologic therapies such as infliximab, anakinra, and ustekinumab carry level 2B recommendations, which Dr. Sayed said will likely influence the availability of these therapies.
Similarly, Nd:YAG laser carries a level 2B recommendation, as does wide excision surgical intervention.
Many of the other treatment modalities explored in the guidelines are not well supported by the literature, according to Dr. Sayed . “The vast majority ... had category C recommendations,” he said. “Some things we tried to evaluate that, really, we can’t give any recommendation on at all because there was no evidence.” He noted that changes in lifestyle and dietary practices are issues patients with HS frequently bring up, but they carry very little evidence of benefit in the literature.
“Even things we use very commonly in HS are often supported by weak evidence because we have to rely on clinical experience. ... There’s just not funding for trials of older drugs or lifestyle interventions,” he said. Treatment mainstays such as tetracycline-class antibiotics, for example, similarly have no large-scale randomized controlled trials to support their use.
Consider comorbidity screening
Treatment is frequently complicated by patient comorbidities, including type 2 diabetes, metabolic syndrome, polycystic ovary syndrome (PCOS), and impaired sexual health, said Dr. Sayed.
“The disease leads to scarring and disfigurement, and can [have a] higher impact on quality of life than almost any other dermatologic disease if you compare them side by side using quality of life measures,” he noted. “We know these patients are more likely to have depression, there are high rates of suicide among these patients. A lot of that has to do with the fact that it’s a chronic disease where there is pain and disfigurement, and patients often grow very, very frustrated in part due to the disease.”
He advised consistent follow-up to ensure patients are not frustrated because of lack of perceived progress.
No one-size-fits-all approach
Dr. Sayed said individualized management is one of the most important parts of taking care of a patient with HS. For example, patients with Hurley stage 1 and Hurley stage 2 variations of the disease may present very differently, and that is the reason why the guidelines do not offer a stepwise treatment algorithm for the disease.
“[The guidelines] have many treatments that may overlap different stages of disease, where those things might need to be used together,” he said. “It takes a lot of discussion with patients about their treatment preferences and listening to whether their disease is progressing or not, whether or not it’s stable, and then trying to figure out whether things like surgery fit into the treatment strategy.”
Despite these recommendations, there may be situations where the answer is not listed in the guidelines. “The guidelines are based on evidence that’s available at the time we review the literature,” he said. “For many patients, they may fail every treatment that’s recommended within the guidelines. There will be times where you have to be creative for patients and go beyond what the guidelines can currently recommend and give patients the treatment that they need even when it seems like all options have been exhausted.”
The authors report relationships with 3M, AbbVie, Adelphi Values, Amgen, BSN, Celgene, Chemocentryx, Coloplast, Galderma, Hidramed Solutions, Hollister, the HS Foundation, Incyte, InflaRx, Integra, Janssen, KCI Inc., Lenicura, Leo, Lilly, The Microdermis Corporation, Novartis, Pfizer, UCB, Valeant, and XBiotech both inside and outside the supported work.
SOURCES: Alikhan A et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.067; Alikhan A et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.068.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
ASCO/ASH Clinical Practice Update: Erythropoiesis-stimulating agents
Erythropoiesis-stimulating agents (ESAs) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin (HgB) has declined to less than 10 g/dL, according to a clinical practice guideline update by the American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH).
Furthermore, ESAs should not be offered to patients with chemotherapy-associated anemia whose cancer treatment is curative in intent, wrote Julia Bohlius, MD, MScPH, of the University of Bern, Switzerland, along with her associates on the expert panel. The report is in the Journal of Clinical Oncology.
The panel members systematically reviewed the body of literature for evidence pertaining to the use of ESAs in patients with cancer. After the review, the team included 15 meta-analyses and 2 randomized controlled trials (RCTs).
“For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer,” they wrote.
The update addressed 10 key clinical questions and provided recommendations based on the available literature and clinical experience.
The addition of iron to treatment with an ESA may provide better hematopoietic response and lower the chances of RBC transfusion, according to the guidelines.
In addition, the review revealed that biosimilars of epoetin alfa could provide safety and efficacy similar to that of other reference products; however, the evidence in cancer is still unclear.
“ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to less than 10 g/dL,” they recommended.
As an alternative to ESAs, they stated that “RBC transfusion is also an option.”
The panel acknowledged that ESAs should not be provided to the majority of patients with nonchemotherapy-related anemia, excluding certain patients with myelodysplastic syndromes.
More information on the guidelines is available on the ASCO and ASH websites.
The study was funded by the American Society of Clinical Oncology. The expert panel reported financial affiliations with AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Novartis, Takeda, and several others.
SOURCE: Bohlius J et al. J Clin Oncol. 2019 Apr 10. doi: 10.1200/JCO.18.02142.
Erythropoiesis-stimulating agents (ESAs) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin (HgB) has declined to less than 10 g/dL, according to a clinical practice guideline update by the American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH).
Furthermore, ESAs should not be offered to patients with chemotherapy-associated anemia whose cancer treatment is curative in intent, wrote Julia Bohlius, MD, MScPH, of the University of Bern, Switzerland, along with her associates on the expert panel. The report is in the Journal of Clinical Oncology.
The panel members systematically reviewed the body of literature for evidence pertaining to the use of ESAs in patients with cancer. After the review, the team included 15 meta-analyses and 2 randomized controlled trials (RCTs).
“For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer,” they wrote.
The update addressed 10 key clinical questions and provided recommendations based on the available literature and clinical experience.
The addition of iron to treatment with an ESA may provide better hematopoietic response and lower the chances of RBC transfusion, according to the guidelines.
In addition, the review revealed that biosimilars of epoetin alfa could provide safety and efficacy similar to that of other reference products; however, the evidence in cancer is still unclear.
“ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to less than 10 g/dL,” they recommended.
As an alternative to ESAs, they stated that “RBC transfusion is also an option.”
The panel acknowledged that ESAs should not be provided to the majority of patients with nonchemotherapy-related anemia, excluding certain patients with myelodysplastic syndromes.
More information on the guidelines is available on the ASCO and ASH websites.
The study was funded by the American Society of Clinical Oncology. The expert panel reported financial affiliations with AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Novartis, Takeda, and several others.
SOURCE: Bohlius J et al. J Clin Oncol. 2019 Apr 10. doi: 10.1200/JCO.18.02142.
Erythropoiesis-stimulating agents (ESAs) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin (HgB) has declined to less than 10 g/dL, according to a clinical practice guideline update by the American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH).
Furthermore, ESAs should not be offered to patients with chemotherapy-associated anemia whose cancer treatment is curative in intent, wrote Julia Bohlius, MD, MScPH, of the University of Bern, Switzerland, along with her associates on the expert panel. The report is in the Journal of Clinical Oncology.
The panel members systematically reviewed the body of literature for evidence pertaining to the use of ESAs in patients with cancer. After the review, the team included 15 meta-analyses and 2 randomized controlled trials (RCTs).
“For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer,” they wrote.
The update addressed 10 key clinical questions and provided recommendations based on the available literature and clinical experience.
The addition of iron to treatment with an ESA may provide better hematopoietic response and lower the chances of RBC transfusion, according to the guidelines.
In addition, the review revealed that biosimilars of epoetin alfa could provide safety and efficacy similar to that of other reference products; however, the evidence in cancer is still unclear.
“ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to less than 10 g/dL,” they recommended.
As an alternative to ESAs, they stated that “RBC transfusion is also an option.”
The panel acknowledged that ESAs should not be provided to the majority of patients with nonchemotherapy-related anemia, excluding certain patients with myelodysplastic syndromes.
More information on the guidelines is available on the ASCO and ASH websites.
The study was funded by the American Society of Clinical Oncology. The expert panel reported financial affiliations with AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Novartis, Takeda, and several others.
SOURCE: Bohlius J et al. J Clin Oncol. 2019 Apr 10. doi: 10.1200/JCO.18.02142.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
EULAR takes SLE guidance to the next level
The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.
The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).
A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.
The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.
Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.
For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.
Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.
The new guidance is also more certain about mycophenolate for renal disease, with a strong recommendation for use as an induction and maintenance agent, with azathioprine the other strong candidate for maintenance. EULAR also made a weak recommendation for mycophenolate with low-dose calcineurin inhibitors in severe nephrotic syndrome, in some circumstances.
For antiphospholipid antibody carriers, EULAR noted that a recent randomized, open-label trial comparing rivaroxaban against warfarin “was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm. Thus, in patients with SLE-antiphospholipid syndrome, “use of novel oral anticoagulants for secondary prevention should be avoided.”
The group notes that management should aim at “remission of disease symptoms and signs, prevention of damage accrual, and minimization of drug side effects, as well as improvement of quality of life.” To that end, it said newly defined low disease-activity states, such as an SLE Disease Activity Index score of 3 or less on antimalarials, are useful to guide treatment, and have comparable rates of remission and flare prevention.
SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089
The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.
The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).
A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.
The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.
Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.
For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.
Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.
The new guidance is also more certain about mycophenolate for renal disease, with a strong recommendation for use as an induction and maintenance agent, with azathioprine the other strong candidate for maintenance. EULAR also made a weak recommendation for mycophenolate with low-dose calcineurin inhibitors in severe nephrotic syndrome, in some circumstances.
For antiphospholipid antibody carriers, EULAR noted that a recent randomized, open-label trial comparing rivaroxaban against warfarin “was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm. Thus, in patients with SLE-antiphospholipid syndrome, “use of novel oral anticoagulants for secondary prevention should be avoided.”
The group notes that management should aim at “remission of disease symptoms and signs, prevention of damage accrual, and minimization of drug side effects, as well as improvement of quality of life.” To that end, it said newly defined low disease-activity states, such as an SLE Disease Activity Index score of 3 or less on antimalarials, are useful to guide treatment, and have comparable rates of remission and flare prevention.
SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089
The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.
The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).
A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.
The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.
Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.
For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.
Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.
The new guidance is also more certain about mycophenolate for renal disease, with a strong recommendation for use as an induction and maintenance agent, with azathioprine the other strong candidate for maintenance. EULAR also made a weak recommendation for mycophenolate with low-dose calcineurin inhibitors in severe nephrotic syndrome, in some circumstances.
For antiphospholipid antibody carriers, EULAR noted that a recent randomized, open-label trial comparing rivaroxaban against warfarin “was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm. Thus, in patients with SLE-antiphospholipid syndrome, “use of novel oral anticoagulants for secondary prevention should be avoided.”
The group notes that management should aim at “remission of disease symptoms and signs, prevention of damage accrual, and minimization of drug side effects, as well as improvement of quality of life.” To that end, it said newly defined low disease-activity states, such as an SLE Disease Activity Index score of 3 or less on antimalarials, are useful to guide treatment, and have comparable rates of remission and flare prevention.
SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089
FROM ANNALS OF THE RHEUMATIC DISEASES
ASCO, CCO issue multiple myeloma treatment guidelines
New clinical practice guidelines, jointly released by two leading cancer organizations, provide nearly 50 specific recommendations for the management of newly diagnosed and relapsed multiple myeloma patients.
The guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) were authored by a panel of 21 experts in medical oncology, surgery, radiation oncology, and advocacy who reviewed 124 relevant studies published between 2005 and 2018.
“The treatment of multiple myeloma has changed significantly in the last 5 years. Since 2015, four new drugs have been approved, thus providing more options and adding to the complexity of treatment options,” the expert panel wrote in the Journal of Clinical Oncology.
The recommendations are intended to put in context recent randomized trials and drug advances, according to the experts, led by cochairs Joseph Mikhael, MD, of City of Hope Cancer Center, Phoenix, and the International Myeloma Foundation, North Hollywood, Calif., and Tom Martin, MD, of the University of California, San Francisco.
Specifically, the recently approved agents include the proteasome inhibitor ixazomib, the histone deacetylase inhibitor panobinostat, and the monoclonal antibodies daratumumab and elotuzumab, directed at CD38 and SLAMF7, respectively.
There are 20 specific recommendations for newly diagnosed, transplant-eligible patients with multiple myeloma; 10 recommendations for newly diagnosed, transplant-ineligible patients; and 16 recommendations related to relapsed disease in the ASCO/CCO guidelines.
All transplant-eligible patients should be offered up-front autologous stem cell transplant (ASCT), according to the guidelines. By contrast, allogeneic transplant is not routinely recommended but “may be considered” in select high-risk patients, and tandem transplant “should not be routinely recommended,” the expert panelists said in their report.
Lenalidomide maintenance therapy should be routinely offered to standard-risk, transplant-eligible patients, according to the panel, whereas bortezomib maintenance could be considered in those who are intolerant of lenalidomide or can’t receive that immunomodulatory drug.
“Evidence is emerging for the use of ixazomib as maintenance therapy and may also be considered,” the panel members said, citing the TOURMALINE-MM3 study results presented at the 2018 annual meeting of the American Society of Hematology and recently published in the Lancet.
Although minimal residual disease (MRD)–negative status is linked to improved outcomes, there is insufficient evidence that MRD can be used today to modify maintenance therapy based on depth of response in transplant-eligible patients, according to the guidelines. Likewise, in transplant-ineligible patients, MRD shouldn’t be used to guide treatment goals in clinical practice, the authors said.
Triplet therapies such as bortezomib, lenalidomide, and dexamethasone (VRd) can be considered for transplant ineligible patients, as can the combination of daratumumab and bortezomib plus melphalan and prednisone that was approved by the Food and Drug Administration in May 2018.
For patients with biochemically relapsed myeloma and high-risk disease – defined as early relapse and presence of high-risk cytogenetics – treatment should begin immediately, whereas close observation may be appropriate for patients with asymptomatic, slowly progressive relapse.
Triplets containing two novel therapies should be administered on first relapse, and should continue until disease progression, the expert panel advised.
If it was not already done after primary induction, ASCT should be offered to relapsed, transplant-eligible myeloma patients.
The expert panel reported numerous financial relationships with industry, including Celgene, Sanofi, AbbVie, TeneoBio, Roche, June Therapeutics, and others.
SOURCE: Mikhael J et al. J Clin Oncol. 2019 Apr 1. doi: 10.1200/JCO.18.02096.
New clinical practice guidelines, jointly released by two leading cancer organizations, provide nearly 50 specific recommendations for the management of newly diagnosed and relapsed multiple myeloma patients.
The guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) were authored by a panel of 21 experts in medical oncology, surgery, radiation oncology, and advocacy who reviewed 124 relevant studies published between 2005 and 2018.
“The treatment of multiple myeloma has changed significantly in the last 5 years. Since 2015, four new drugs have been approved, thus providing more options and adding to the complexity of treatment options,” the expert panel wrote in the Journal of Clinical Oncology.
The recommendations are intended to put in context recent randomized trials and drug advances, according to the experts, led by cochairs Joseph Mikhael, MD, of City of Hope Cancer Center, Phoenix, and the International Myeloma Foundation, North Hollywood, Calif., and Tom Martin, MD, of the University of California, San Francisco.
Specifically, the recently approved agents include the proteasome inhibitor ixazomib, the histone deacetylase inhibitor panobinostat, and the monoclonal antibodies daratumumab and elotuzumab, directed at CD38 and SLAMF7, respectively.
There are 20 specific recommendations for newly diagnosed, transplant-eligible patients with multiple myeloma; 10 recommendations for newly diagnosed, transplant-ineligible patients; and 16 recommendations related to relapsed disease in the ASCO/CCO guidelines.
All transplant-eligible patients should be offered up-front autologous stem cell transplant (ASCT), according to the guidelines. By contrast, allogeneic transplant is not routinely recommended but “may be considered” in select high-risk patients, and tandem transplant “should not be routinely recommended,” the expert panelists said in their report.
Lenalidomide maintenance therapy should be routinely offered to standard-risk, transplant-eligible patients, according to the panel, whereas bortezomib maintenance could be considered in those who are intolerant of lenalidomide or can’t receive that immunomodulatory drug.
“Evidence is emerging for the use of ixazomib as maintenance therapy and may also be considered,” the panel members said, citing the TOURMALINE-MM3 study results presented at the 2018 annual meeting of the American Society of Hematology and recently published in the Lancet.
Although minimal residual disease (MRD)–negative status is linked to improved outcomes, there is insufficient evidence that MRD can be used today to modify maintenance therapy based on depth of response in transplant-eligible patients, according to the guidelines. Likewise, in transplant-ineligible patients, MRD shouldn’t be used to guide treatment goals in clinical practice, the authors said.
Triplet therapies such as bortezomib, lenalidomide, and dexamethasone (VRd) can be considered for transplant ineligible patients, as can the combination of daratumumab and bortezomib plus melphalan and prednisone that was approved by the Food and Drug Administration in May 2018.
For patients with biochemically relapsed myeloma and high-risk disease – defined as early relapse and presence of high-risk cytogenetics – treatment should begin immediately, whereas close observation may be appropriate for patients with asymptomatic, slowly progressive relapse.
Triplets containing two novel therapies should be administered on first relapse, and should continue until disease progression, the expert panel advised.
If it was not already done after primary induction, ASCT should be offered to relapsed, transplant-eligible myeloma patients.
The expert panel reported numerous financial relationships with industry, including Celgene, Sanofi, AbbVie, TeneoBio, Roche, June Therapeutics, and others.
SOURCE: Mikhael J et al. J Clin Oncol. 2019 Apr 1. doi: 10.1200/JCO.18.02096.
New clinical practice guidelines, jointly released by two leading cancer organizations, provide nearly 50 specific recommendations for the management of newly diagnosed and relapsed multiple myeloma patients.
The guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) were authored by a panel of 21 experts in medical oncology, surgery, radiation oncology, and advocacy who reviewed 124 relevant studies published between 2005 and 2018.
“The treatment of multiple myeloma has changed significantly in the last 5 years. Since 2015, four new drugs have been approved, thus providing more options and adding to the complexity of treatment options,” the expert panel wrote in the Journal of Clinical Oncology.
The recommendations are intended to put in context recent randomized trials and drug advances, according to the experts, led by cochairs Joseph Mikhael, MD, of City of Hope Cancer Center, Phoenix, and the International Myeloma Foundation, North Hollywood, Calif., and Tom Martin, MD, of the University of California, San Francisco.
Specifically, the recently approved agents include the proteasome inhibitor ixazomib, the histone deacetylase inhibitor panobinostat, and the monoclonal antibodies daratumumab and elotuzumab, directed at CD38 and SLAMF7, respectively.
There are 20 specific recommendations for newly diagnosed, transplant-eligible patients with multiple myeloma; 10 recommendations for newly diagnosed, transplant-ineligible patients; and 16 recommendations related to relapsed disease in the ASCO/CCO guidelines.
All transplant-eligible patients should be offered up-front autologous stem cell transplant (ASCT), according to the guidelines. By contrast, allogeneic transplant is not routinely recommended but “may be considered” in select high-risk patients, and tandem transplant “should not be routinely recommended,” the expert panelists said in their report.
Lenalidomide maintenance therapy should be routinely offered to standard-risk, transplant-eligible patients, according to the panel, whereas bortezomib maintenance could be considered in those who are intolerant of lenalidomide or can’t receive that immunomodulatory drug.
“Evidence is emerging for the use of ixazomib as maintenance therapy and may also be considered,” the panel members said, citing the TOURMALINE-MM3 study results presented at the 2018 annual meeting of the American Society of Hematology and recently published in the Lancet.
Although minimal residual disease (MRD)–negative status is linked to improved outcomes, there is insufficient evidence that MRD can be used today to modify maintenance therapy based on depth of response in transplant-eligible patients, according to the guidelines. Likewise, in transplant-ineligible patients, MRD shouldn’t be used to guide treatment goals in clinical practice, the authors said.
Triplet therapies such as bortezomib, lenalidomide, and dexamethasone (VRd) can be considered for transplant ineligible patients, as can the combination of daratumumab and bortezomib plus melphalan and prednisone that was approved by the Food and Drug Administration in May 2018.
For patients with biochemically relapsed myeloma and high-risk disease – defined as early relapse and presence of high-risk cytogenetics – treatment should begin immediately, whereas close observation may be appropriate for patients with asymptomatic, slowly progressive relapse.
Triplets containing two novel therapies should be administered on first relapse, and should continue until disease progression, the expert panel advised.
If it was not already done after primary induction, ASCT should be offered to relapsed, transplant-eligible myeloma patients.
The expert panel reported numerous financial relationships with industry, including Celgene, Sanofi, AbbVie, TeneoBio, Roche, June Therapeutics, and others.
SOURCE: Mikhael J et al. J Clin Oncol. 2019 Apr 1. doi: 10.1200/JCO.18.02096.
FROM THE JOURNAL OF CLINICAL ONCOLOGY