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Appendix linked to Parkinson’s disease in series of unexpected findings
Appendectomy has been associated with a reduced risk of Parkinson’s disease (PD), which supports the potential for a reservoir of aggregated alpha-synuclein in the appendix to affect risk of the condition, according to new epidemiologic and translational evidence from two data sets that promotes a new and emerging theory for PD etiology.
When placed into the context of other recent studies, these epidemiologic data “point to the appendix as a site of origin for Parkinson’s and provide a path forward for devising new treatment strategies,” reported senior author Viviane Labrie, PhD, of the Van Andel Research Institute (VARI) in Grand Rapids, Mich.
The epidemiologic data was the most recent step in a series of findings summarized in a newly published paper in Science Translational Medicine. As the researchers explained, it is relevant to a separate body of evidence that alpha-synuclein, a protein that serves as the hallmark of PD when it appears in Lewy bodies, can be isolated in the nerve fibers and nerve cells of the appendix.
“We have shown that alpha-synuclein proteins, including the truncated forms observed in Lewy bodies, are abundant in the appendix,” reported first author Bryan A. Killinger, PhD, also at VARI, in a press teleconference. He said this finding is likely to explain the reduced risk of PD from appendectomy.
In the largest of the epidemiologic studies, the effect of appendectomy on subsequent risk of PD was evaluated through the health records from more than 1.6 million individuals in Sweden. The incidence of PD was found to be 19.3% lower among 551,647 patients who had an appendectomy, compared with controls.
In addition, the data showed that when PD did occur after appendectomy, it was delayed on average by 3.6 years. It is notable that appendectomy was not associated with protection from PD in patients with a familial link to PD, a group they said comprises less than 10% of cases.
In patients with PD, nonmotor symptoms often include GI tract dysfunction, which can, in some cases, be part of a prodromal presentation that precedes the onset of classical PD symptoms by several years, the authors reported. However, the new research upends previous conceptions of disease. The demonstration of abundant alpha-synuclein in the appendix coupled with the protective effect of appendectomy, suggests that PD may originate in the GI tract and then spread to the central nervous system (CNS) rather than the other way around.
“The vermiform appendix was once considered to be an unnecessary organ. Although there is now good evidence that the appendix plays a major role in the regulation of the immune system, including the regulation of gut bacteria, our work suggests it is also mediates risk of Parkinson’s,” Dr. Labrie said in the teleconference.
In the paper, numerous pieces of the puzzle are brought together to suggest that alpha-synuclein in the appendix is linked to alpha-synuclein in the CNS. Many of the findings along this investigative pathway were described as surprising. For example, immunohistochemistry studies revealed high amounts of alpha-synuclein in nearly every sample of appendiceal tissue examined, including normal and inflamed tissue, tissue from individuals with PD and those without, and tissues from young and old individuals.
“The normal tissue, as well as appendiceal tissue from PD patients, contained high levels of alpha-synuclein in the truncated forms analogous to those seen in Lewy body pathology,” Dr. Killinger said. Based on these and other findings, he believes that alpha-synuclein in the appendix forms a reservoir for seeding the aggregates involved in the pathology of PD, although he acknowledged that it is not yet clear how the proteins in the appendix find their way to the brain.
From these data, it appears that most individuals with an intact appendix have alpha-synuclein in the nerve fibers, but Dr. Labrie pointed out that the only about 1% of the population develops PD. She speculated that there is “some confluence of events,” such as an environmental trigger altering the GI microbiome, that mediates ultimate risk of PD, but she noted that these events may take place decades before signs and symptoms of PD develop. The data appear to be a substantial reorientation in understanding PD.
“We have shown that the appendix is a hub for the accumulation of clumped forms of alpha-synuclein proteins, which are implicated in Parkinson’s,” Dr. Killinger said. “This knowledge will be invaluable as we explore new prevention and treatment strategies.”
The research was funded by a variety of governmental and private grants to individual authors. Dr. Killinger and Dr. Labrie report no financial relationships relevant to this study.
SOURCE: Killinger BA et al. Sci Transl Med. 2018;10:eaar5380.
Appendectomy has been associated with a reduced risk of Parkinson’s disease (PD), which supports the potential for a reservoir of aggregated alpha-synuclein in the appendix to affect risk of the condition, according to new epidemiologic and translational evidence from two data sets that promotes a new and emerging theory for PD etiology.
When placed into the context of other recent studies, these epidemiologic data “point to the appendix as a site of origin for Parkinson’s and provide a path forward for devising new treatment strategies,” reported senior author Viviane Labrie, PhD, of the Van Andel Research Institute (VARI) in Grand Rapids, Mich.
The epidemiologic data was the most recent step in a series of findings summarized in a newly published paper in Science Translational Medicine. As the researchers explained, it is relevant to a separate body of evidence that alpha-synuclein, a protein that serves as the hallmark of PD when it appears in Lewy bodies, can be isolated in the nerve fibers and nerve cells of the appendix.
“We have shown that alpha-synuclein proteins, including the truncated forms observed in Lewy bodies, are abundant in the appendix,” reported first author Bryan A. Killinger, PhD, also at VARI, in a press teleconference. He said this finding is likely to explain the reduced risk of PD from appendectomy.
In the largest of the epidemiologic studies, the effect of appendectomy on subsequent risk of PD was evaluated through the health records from more than 1.6 million individuals in Sweden. The incidence of PD was found to be 19.3% lower among 551,647 patients who had an appendectomy, compared with controls.
In addition, the data showed that when PD did occur after appendectomy, it was delayed on average by 3.6 years. It is notable that appendectomy was not associated with protection from PD in patients with a familial link to PD, a group they said comprises less than 10% of cases.
In patients with PD, nonmotor symptoms often include GI tract dysfunction, which can, in some cases, be part of a prodromal presentation that precedes the onset of classical PD symptoms by several years, the authors reported. However, the new research upends previous conceptions of disease. The demonstration of abundant alpha-synuclein in the appendix coupled with the protective effect of appendectomy, suggests that PD may originate in the GI tract and then spread to the central nervous system (CNS) rather than the other way around.
“The vermiform appendix was once considered to be an unnecessary organ. Although there is now good evidence that the appendix plays a major role in the regulation of the immune system, including the regulation of gut bacteria, our work suggests it is also mediates risk of Parkinson’s,” Dr. Labrie said in the teleconference.
In the paper, numerous pieces of the puzzle are brought together to suggest that alpha-synuclein in the appendix is linked to alpha-synuclein in the CNS. Many of the findings along this investigative pathway were described as surprising. For example, immunohistochemistry studies revealed high amounts of alpha-synuclein in nearly every sample of appendiceal tissue examined, including normal and inflamed tissue, tissue from individuals with PD and those without, and tissues from young and old individuals.
“The normal tissue, as well as appendiceal tissue from PD patients, contained high levels of alpha-synuclein in the truncated forms analogous to those seen in Lewy body pathology,” Dr. Killinger said. Based on these and other findings, he believes that alpha-synuclein in the appendix forms a reservoir for seeding the aggregates involved in the pathology of PD, although he acknowledged that it is not yet clear how the proteins in the appendix find their way to the brain.
From these data, it appears that most individuals with an intact appendix have alpha-synuclein in the nerve fibers, but Dr. Labrie pointed out that the only about 1% of the population develops PD. She speculated that there is “some confluence of events,” such as an environmental trigger altering the GI microbiome, that mediates ultimate risk of PD, but she noted that these events may take place decades before signs and symptoms of PD develop. The data appear to be a substantial reorientation in understanding PD.
“We have shown that the appendix is a hub for the accumulation of clumped forms of alpha-synuclein proteins, which are implicated in Parkinson’s,” Dr. Killinger said. “This knowledge will be invaluable as we explore new prevention and treatment strategies.”
The research was funded by a variety of governmental and private grants to individual authors. Dr. Killinger and Dr. Labrie report no financial relationships relevant to this study.
SOURCE: Killinger BA et al. Sci Transl Med. 2018;10:eaar5380.
Appendectomy has been associated with a reduced risk of Parkinson’s disease (PD), which supports the potential for a reservoir of aggregated alpha-synuclein in the appendix to affect risk of the condition, according to new epidemiologic and translational evidence from two data sets that promotes a new and emerging theory for PD etiology.
When placed into the context of other recent studies, these epidemiologic data “point to the appendix as a site of origin for Parkinson’s and provide a path forward for devising new treatment strategies,” reported senior author Viviane Labrie, PhD, of the Van Andel Research Institute (VARI) in Grand Rapids, Mich.
The epidemiologic data was the most recent step in a series of findings summarized in a newly published paper in Science Translational Medicine. As the researchers explained, it is relevant to a separate body of evidence that alpha-synuclein, a protein that serves as the hallmark of PD when it appears in Lewy bodies, can be isolated in the nerve fibers and nerve cells of the appendix.
“We have shown that alpha-synuclein proteins, including the truncated forms observed in Lewy bodies, are abundant in the appendix,” reported first author Bryan A. Killinger, PhD, also at VARI, in a press teleconference. He said this finding is likely to explain the reduced risk of PD from appendectomy.
In the largest of the epidemiologic studies, the effect of appendectomy on subsequent risk of PD was evaluated through the health records from more than 1.6 million individuals in Sweden. The incidence of PD was found to be 19.3% lower among 551,647 patients who had an appendectomy, compared with controls.
In addition, the data showed that when PD did occur after appendectomy, it was delayed on average by 3.6 years. It is notable that appendectomy was not associated with protection from PD in patients with a familial link to PD, a group they said comprises less than 10% of cases.
In patients with PD, nonmotor symptoms often include GI tract dysfunction, which can, in some cases, be part of a prodromal presentation that precedes the onset of classical PD symptoms by several years, the authors reported. However, the new research upends previous conceptions of disease. The demonstration of abundant alpha-synuclein in the appendix coupled with the protective effect of appendectomy, suggests that PD may originate in the GI tract and then spread to the central nervous system (CNS) rather than the other way around.
“The vermiform appendix was once considered to be an unnecessary organ. Although there is now good evidence that the appendix plays a major role in the regulation of the immune system, including the regulation of gut bacteria, our work suggests it is also mediates risk of Parkinson’s,” Dr. Labrie said in the teleconference.
In the paper, numerous pieces of the puzzle are brought together to suggest that alpha-synuclein in the appendix is linked to alpha-synuclein in the CNS. Many of the findings along this investigative pathway were described as surprising. For example, immunohistochemistry studies revealed high amounts of alpha-synuclein in nearly every sample of appendiceal tissue examined, including normal and inflamed tissue, tissue from individuals with PD and those without, and tissues from young and old individuals.
“The normal tissue, as well as appendiceal tissue from PD patients, contained high levels of alpha-synuclein in the truncated forms analogous to those seen in Lewy body pathology,” Dr. Killinger said. Based on these and other findings, he believes that alpha-synuclein in the appendix forms a reservoir for seeding the aggregates involved in the pathology of PD, although he acknowledged that it is not yet clear how the proteins in the appendix find their way to the brain.
From these data, it appears that most individuals with an intact appendix have alpha-synuclein in the nerve fibers, but Dr. Labrie pointed out that the only about 1% of the population develops PD. She speculated that there is “some confluence of events,” such as an environmental trigger altering the GI microbiome, that mediates ultimate risk of PD, but she noted that these events may take place decades before signs and symptoms of PD develop. The data appear to be a substantial reorientation in understanding PD.
“We have shown that the appendix is a hub for the accumulation of clumped forms of alpha-synuclein proteins, which are implicated in Parkinson’s,” Dr. Killinger said. “This knowledge will be invaluable as we explore new prevention and treatment strategies.”
The research was funded by a variety of governmental and private grants to individual authors. Dr. Killinger and Dr. Labrie report no financial relationships relevant to this study.
SOURCE: Killinger BA et al. Sci Transl Med. 2018;10:eaar5380.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point:
Major finding: A 19.3% reduction in risk of PD from appendectomy may relate to alpha-synuclein in the appendix.
Study details: Series of related epidemiologic and translational studies.
Disclosures: The research was funded by a variety of governmental and private grants to individual authors. Dr. Killinger and Dr. Labrie report no financial relationships relevant to this study.
Source: Killinger BA et al. Sci Transl Med. 2018;10:eaar5380.
Brisk walking may decrease TKR risk in OA
CHICAGO – according to a new analysis of data from the National Institutes of Health-sponsored Osteoarthritis Initiative.
Whether walking increases or decreases the risk of structural deterioration and total knee replacement (TKR) in patients with knee osteoarthritis has been a controversial topic marked by conflicting data. That’s probably because prior studies haven’t taken into account walking intensity, Hiral Master said at the annual meeting of the American College of Rheumatology.
Ms. Master, a PhD candidate in physical therapy at the University of Delaware, Newark, presented a study of 1,854 patients with knee osteoarthritis who participated in the Osteoarthritis Initiative, all of whom had worn an accelerometer. This permitted calculation of time spent walking at various intensities. Subjects spent an average of 459 minutes per day not walking and 8 minutes walking at moderate to vigorous intensity, defined as a cadence of more than 100 steps per minute.
During 5 years of follow-up, the incidence of TKR was 6%. In this video interview, Ms. Master explains that patients who replaced 5 minutes of not walking with 5 minutes of brisk walking daily had an adjusted 14% reduction in the risk of TKR. A dose-response was evident, with more minutes of moderate to vigorous walking being associated with progressively larger reductions in the risk of this major surgery. Walking at a cadence of less than 100 steps per minute, regardless of duration, was nonprotective.
SOURCE: Master H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1166.
CHICAGO – according to a new analysis of data from the National Institutes of Health-sponsored Osteoarthritis Initiative.
Whether walking increases or decreases the risk of structural deterioration and total knee replacement (TKR) in patients with knee osteoarthritis has been a controversial topic marked by conflicting data. That’s probably because prior studies haven’t taken into account walking intensity, Hiral Master said at the annual meeting of the American College of Rheumatology.
Ms. Master, a PhD candidate in physical therapy at the University of Delaware, Newark, presented a study of 1,854 patients with knee osteoarthritis who participated in the Osteoarthritis Initiative, all of whom had worn an accelerometer. This permitted calculation of time spent walking at various intensities. Subjects spent an average of 459 minutes per day not walking and 8 minutes walking at moderate to vigorous intensity, defined as a cadence of more than 100 steps per minute.
During 5 years of follow-up, the incidence of TKR was 6%. In this video interview, Ms. Master explains that patients who replaced 5 minutes of not walking with 5 minutes of brisk walking daily had an adjusted 14% reduction in the risk of TKR. A dose-response was evident, with more minutes of moderate to vigorous walking being associated with progressively larger reductions in the risk of this major surgery. Walking at a cadence of less than 100 steps per minute, regardless of duration, was nonprotective.
SOURCE: Master H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1166.
CHICAGO – according to a new analysis of data from the National Institutes of Health-sponsored Osteoarthritis Initiative.
Whether walking increases or decreases the risk of structural deterioration and total knee replacement (TKR) in patients with knee osteoarthritis has been a controversial topic marked by conflicting data. That’s probably because prior studies haven’t taken into account walking intensity, Hiral Master said at the annual meeting of the American College of Rheumatology.
Ms. Master, a PhD candidate in physical therapy at the University of Delaware, Newark, presented a study of 1,854 patients with knee osteoarthritis who participated in the Osteoarthritis Initiative, all of whom had worn an accelerometer. This permitted calculation of time spent walking at various intensities. Subjects spent an average of 459 minutes per day not walking and 8 minutes walking at moderate to vigorous intensity, defined as a cadence of more than 100 steps per minute.
During 5 years of follow-up, the incidence of TKR was 6%. In this video interview, Ms. Master explains that patients who replaced 5 minutes of not walking with 5 minutes of brisk walking daily had an adjusted 14% reduction in the risk of TKR. A dose-response was evident, with more minutes of moderate to vigorous walking being associated with progressively larger reductions in the risk of this major surgery. Walking at a cadence of less than 100 steps per minute, regardless of duration, was nonprotective.
SOURCE: Master H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1166.
REPORTING FROM THE ACR ANNUAL MEETING
Antiphospholipid antibodies are surprisingly common in first-MI patients
CHICAGO – Patients with a first MI were nearly nine times more likely to have detectable IgG antiphospholipid antibodies than were matched controls in a cross-sectional cohort study, Elisabet Svenungsson, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
Her case-control study included 805 Swedish patients tested for antiphospholipid antibodies 6-10 weeks after experiencing their first MI and an equal number of age-, sex-, and location-matched controls. Prior to their MIs, none of the patients had been diagnosed with antiphospholipid syndrome, which requires both positive antiphospholipid antibodies and a vascular thrombotic event or obstetric morbidity.
A positive test for IgG anti-cardiolipin antibody was present in 10.9% of the first-MI patients, compared with 0.9% of controls. Similarly, 10.4% of acute MI patients and 0.9% of controls were positive for anti-beta2-glycoprotein-1 antibodies. Most patients who tested positive for one were positive for both. Thus, it’s possible that IgG antiphospholipid antibody positivity is an important silent risk factor that’s present in 1 in 10 MI patients, according to Dr. Svenungsson, professor of rheumatology at the Karolinska Institute in Stockholm.
If these results are confirmed and expanded upon in additional studies, testing for antiphospholipid antibodies could become part of the routine care in patients with an acute MI. Those who test positive would meet the criteria for antiphospholipid syndrome and qualify for long-term oral anticoagulation to reduce their elevated risk of further vascular events, she explained in this video interview.
The study was published in Annals of Internal Medicine simultaneously with the presentation at the ACR annual meeting (Ann Int Med. 2018 Oct 23. doi: 10.7326/M18-2130).
SOURCE: Grosso G et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 855.
CHICAGO – Patients with a first MI were nearly nine times more likely to have detectable IgG antiphospholipid antibodies than were matched controls in a cross-sectional cohort study, Elisabet Svenungsson, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
Her case-control study included 805 Swedish patients tested for antiphospholipid antibodies 6-10 weeks after experiencing their first MI and an equal number of age-, sex-, and location-matched controls. Prior to their MIs, none of the patients had been diagnosed with antiphospholipid syndrome, which requires both positive antiphospholipid antibodies and a vascular thrombotic event or obstetric morbidity.
A positive test for IgG anti-cardiolipin antibody was present in 10.9% of the first-MI patients, compared with 0.9% of controls. Similarly, 10.4% of acute MI patients and 0.9% of controls were positive for anti-beta2-glycoprotein-1 antibodies. Most patients who tested positive for one were positive for both. Thus, it’s possible that IgG antiphospholipid antibody positivity is an important silent risk factor that’s present in 1 in 10 MI patients, according to Dr. Svenungsson, professor of rheumatology at the Karolinska Institute in Stockholm.
If these results are confirmed and expanded upon in additional studies, testing for antiphospholipid antibodies could become part of the routine care in patients with an acute MI. Those who test positive would meet the criteria for antiphospholipid syndrome and qualify for long-term oral anticoagulation to reduce their elevated risk of further vascular events, she explained in this video interview.
The study was published in Annals of Internal Medicine simultaneously with the presentation at the ACR annual meeting (Ann Int Med. 2018 Oct 23. doi: 10.7326/M18-2130).
SOURCE: Grosso G et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 855.
CHICAGO – Patients with a first MI were nearly nine times more likely to have detectable IgG antiphospholipid antibodies than were matched controls in a cross-sectional cohort study, Elisabet Svenungsson, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
Her case-control study included 805 Swedish patients tested for antiphospholipid antibodies 6-10 weeks after experiencing their first MI and an equal number of age-, sex-, and location-matched controls. Prior to their MIs, none of the patients had been diagnosed with antiphospholipid syndrome, which requires both positive antiphospholipid antibodies and a vascular thrombotic event or obstetric morbidity.
A positive test for IgG anti-cardiolipin antibody was present in 10.9% of the first-MI patients, compared with 0.9% of controls. Similarly, 10.4% of acute MI patients and 0.9% of controls were positive for anti-beta2-glycoprotein-1 antibodies. Most patients who tested positive for one were positive for both. Thus, it’s possible that IgG antiphospholipid antibody positivity is an important silent risk factor that’s present in 1 in 10 MI patients, according to Dr. Svenungsson, professor of rheumatology at the Karolinska Institute in Stockholm.
If these results are confirmed and expanded upon in additional studies, testing for antiphospholipid antibodies could become part of the routine care in patients with an acute MI. Those who test positive would meet the criteria for antiphospholipid syndrome and qualify for long-term oral anticoagulation to reduce their elevated risk of further vascular events, she explained in this video interview.
The study was published in Annals of Internal Medicine simultaneously with the presentation at the ACR annual meeting (Ann Int Med. 2018 Oct 23. doi: 10.7326/M18-2130).
SOURCE: Grosso G et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 855.
REPORTING FROM THE ACR ANNUAL MEETING
Technology offers new tools, challenges for rare-disease patients
WASHINGTON – Genetic developments may create a new medical model for patients with rare diseases and the doctors who treat them, according to Marshall Summar, MD, chief of genetics and metabolism at Children’s National Medical Center in Washington, D.C.
In an interview at the NORD Rare Summit, held by the National Organization for Rare Disorders, Dr. Summar and Peter L. Saltonstall, president and CEO of NORD, discussed hot topics in the rare disease field. Those include new knowledge of the natural history of rare diseases, made possible by the creation of patient databases and the expansion of genetic technology. In addition, some DNA therapies “are finally crossing the finish line,” said Dr. Summar. That means clinicians will be looking at some rare diseases as acute conditions rather than chronic.
However, patients with rare diseases continue to face challenges in terms of the need for prior authorization and for drug access. One of NORD’s missions is to help patients access treatment. “We are seeing these prior authorizations take weeks or even longer,” Mr. Saltonstall said – and meanwhile, patients aren’t receiving therapy.
Visit rarediseases.org for more information about NORD’s ongoing research and advocacy efforts.
Dr. Summar and Mr. Saltonstall had no financial conflicts to disclose.
WASHINGTON – Genetic developments may create a new medical model for patients with rare diseases and the doctors who treat them, according to Marshall Summar, MD, chief of genetics and metabolism at Children’s National Medical Center in Washington, D.C.
In an interview at the NORD Rare Summit, held by the National Organization for Rare Disorders, Dr. Summar and Peter L. Saltonstall, president and CEO of NORD, discussed hot topics in the rare disease field. Those include new knowledge of the natural history of rare diseases, made possible by the creation of patient databases and the expansion of genetic technology. In addition, some DNA therapies “are finally crossing the finish line,” said Dr. Summar. That means clinicians will be looking at some rare diseases as acute conditions rather than chronic.
However, patients with rare diseases continue to face challenges in terms of the need for prior authorization and for drug access. One of NORD’s missions is to help patients access treatment. “We are seeing these prior authorizations take weeks or even longer,” Mr. Saltonstall said – and meanwhile, patients aren’t receiving therapy.
Visit rarediseases.org for more information about NORD’s ongoing research and advocacy efforts.
Dr. Summar and Mr. Saltonstall had no financial conflicts to disclose.
WASHINGTON – Genetic developments may create a new medical model for patients with rare diseases and the doctors who treat them, according to Marshall Summar, MD, chief of genetics and metabolism at Children’s National Medical Center in Washington, D.C.
In an interview at the NORD Rare Summit, held by the National Organization for Rare Disorders, Dr. Summar and Peter L. Saltonstall, president and CEO of NORD, discussed hot topics in the rare disease field. Those include new knowledge of the natural history of rare diseases, made possible by the creation of patient databases and the expansion of genetic technology. In addition, some DNA therapies “are finally crossing the finish line,” said Dr. Summar. That means clinicians will be looking at some rare diseases as acute conditions rather than chronic.
However, patients with rare diseases continue to face challenges in terms of the need for prior authorization and for drug access. One of NORD’s missions is to help patients access treatment. “We are seeing these prior authorizations take weeks or even longer,” Mr. Saltonstall said – and meanwhile, patients aren’t receiving therapy.
Visit rarediseases.org for more information about NORD’s ongoing research and advocacy efforts.
Dr. Summar and Mr. Saltonstall had no financial conflicts to disclose.
REPORTING FROM NORD SUMMIT 2018
Education and support enhance care for rare-disease patients
WASHINGTON – Physicians in primary and specialty care can provide guidance and support to patients with rare diseases by educating themselves about the resources available, according to Tim Boyd, director of state policy for the National Organization for Rare Disorders (NORD).
In an interview at the NORD Rare Summit, held by the National Organization for Rare Disorders, Mr. Boyd and Melinda Burnworth, PharmD, a pharmacist and NORD state volunteer from Arizona, discussed challenges faced by patients with rare diseases, including securing a correct diagnosis, accessing medication, and managing treatment going forward.
Physicians who understand some of the barriers to medication access can help advocate for their patients, explained Mr. Boyd, and those who know about resources for rare disorders can help make a diagnosis.
“All health care providers have an opportunity to enhance care for patients with rare disorders,” said Dr. Burnworth, author of the Rare Disease eResource Guide, available through the American Society of Health-System Pharmacists. Visit rarediseases.org for more information about NORD’s ongoing research and advocacy efforts.
Mr. Boyd and Dr. Burnworth had no financial conflicts to disclose.
WASHINGTON – Physicians in primary and specialty care can provide guidance and support to patients with rare diseases by educating themselves about the resources available, according to Tim Boyd, director of state policy for the National Organization for Rare Disorders (NORD).
In an interview at the NORD Rare Summit, held by the National Organization for Rare Disorders, Mr. Boyd and Melinda Burnworth, PharmD, a pharmacist and NORD state volunteer from Arizona, discussed challenges faced by patients with rare diseases, including securing a correct diagnosis, accessing medication, and managing treatment going forward.
Physicians who understand some of the barriers to medication access can help advocate for their patients, explained Mr. Boyd, and those who know about resources for rare disorders can help make a diagnosis.
“All health care providers have an opportunity to enhance care for patients with rare disorders,” said Dr. Burnworth, author of the Rare Disease eResource Guide, available through the American Society of Health-System Pharmacists. Visit rarediseases.org for more information about NORD’s ongoing research and advocacy efforts.
Mr. Boyd and Dr. Burnworth had no financial conflicts to disclose.
WASHINGTON – Physicians in primary and specialty care can provide guidance and support to patients with rare diseases by educating themselves about the resources available, according to Tim Boyd, director of state policy for the National Organization for Rare Disorders (NORD).
In an interview at the NORD Rare Summit, held by the National Organization for Rare Disorders, Mr. Boyd and Melinda Burnworth, PharmD, a pharmacist and NORD state volunteer from Arizona, discussed challenges faced by patients with rare diseases, including securing a correct diagnosis, accessing medication, and managing treatment going forward.
Physicians who understand some of the barriers to medication access can help advocate for their patients, explained Mr. Boyd, and those who know about resources for rare disorders can help make a diagnosis.
“All health care providers have an opportunity to enhance care for patients with rare disorders,” said Dr. Burnworth, author of the Rare Disease eResource Guide, available through the American Society of Health-System Pharmacists. Visit rarediseases.org for more information about NORD’s ongoing research and advocacy efforts.
Mr. Boyd and Dr. Burnworth had no financial conflicts to disclose.
REPORTING FROM NORD SUMMIT 2018
Drafts of new classification criteria presented for GCA, Takayasu’s arteritis
CHICAGO – Drafts of new classification criteria for giant cell arteritis and Takayasu’s arteritis developed by the American College of Rheumatology and the European League Against Rheumatism (EULAR) reflect the increasingly important role of advanced vascular imaging in the diagnosis and management of large-vessel vasculitis, according to Peter A. Merkel, MD.
The drafts, which are the result of a multiyear collaboration between the ACR and EULAR, were presented at the annual meeting of the ACR and will be submitted to the ACR/EULAR committee overseeing the work for comprehensive review and possible revisions. Once endorsed, the new criteria will replace the “extremely important,” but outdated, existing classification criteria, which were published in 1990.
“What we’ve done is, rather than purely revise the 1990 [criteria], we’ve started again from scratch ... with a great number of cases from a wide variety of centers throughout the world. This was a very large international effort ... really a great community effort in the field of rheumatology,” Dr. Merkel, professor and chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, and one of the chief investigators for the project, said in a video interview.
The new criteria will allow for better classification of patients with giant cell arteritis versus Takayasu’s arteritis versus another form of vasculitis, he said, noting that advances in imaging that allow for “more enriched data with which to make decisions” play a large role.
However, the new criteria are not meant to be used for diagnosis, but to “sort out among the different types of vasculitis,” he said.
“It provides awareness and it provides a tool, especially for research investigation, but that seeps out into the broader community,” he added.
Dr. Merkel reported having no disclosures.
SOURCE: Merkel PA et al. ACR Annual Meeting, Presentation 5T116.
CHICAGO – Drafts of new classification criteria for giant cell arteritis and Takayasu’s arteritis developed by the American College of Rheumatology and the European League Against Rheumatism (EULAR) reflect the increasingly important role of advanced vascular imaging in the diagnosis and management of large-vessel vasculitis, according to Peter A. Merkel, MD.
The drafts, which are the result of a multiyear collaboration between the ACR and EULAR, were presented at the annual meeting of the ACR and will be submitted to the ACR/EULAR committee overseeing the work for comprehensive review and possible revisions. Once endorsed, the new criteria will replace the “extremely important,” but outdated, existing classification criteria, which were published in 1990.
“What we’ve done is, rather than purely revise the 1990 [criteria], we’ve started again from scratch ... with a great number of cases from a wide variety of centers throughout the world. This was a very large international effort ... really a great community effort in the field of rheumatology,” Dr. Merkel, professor and chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, and one of the chief investigators for the project, said in a video interview.
The new criteria will allow for better classification of patients with giant cell arteritis versus Takayasu’s arteritis versus another form of vasculitis, he said, noting that advances in imaging that allow for “more enriched data with which to make decisions” play a large role.
However, the new criteria are not meant to be used for diagnosis, but to “sort out among the different types of vasculitis,” he said.
“It provides awareness and it provides a tool, especially for research investigation, but that seeps out into the broader community,” he added.
Dr. Merkel reported having no disclosures.
SOURCE: Merkel PA et al. ACR Annual Meeting, Presentation 5T116.
CHICAGO – Drafts of new classification criteria for giant cell arteritis and Takayasu’s arteritis developed by the American College of Rheumatology and the European League Against Rheumatism (EULAR) reflect the increasingly important role of advanced vascular imaging in the diagnosis and management of large-vessel vasculitis, according to Peter A. Merkel, MD.
The drafts, which are the result of a multiyear collaboration between the ACR and EULAR, were presented at the annual meeting of the ACR and will be submitted to the ACR/EULAR committee overseeing the work for comprehensive review and possible revisions. Once endorsed, the new criteria will replace the “extremely important,” but outdated, existing classification criteria, which were published in 1990.
“What we’ve done is, rather than purely revise the 1990 [criteria], we’ve started again from scratch ... with a great number of cases from a wide variety of centers throughout the world. This was a very large international effort ... really a great community effort in the field of rheumatology,” Dr. Merkel, professor and chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, and one of the chief investigators for the project, said in a video interview.
The new criteria will allow for better classification of patients with giant cell arteritis versus Takayasu’s arteritis versus another form of vasculitis, he said, noting that advances in imaging that allow for “more enriched data with which to make decisions” play a large role.
However, the new criteria are not meant to be used for diagnosis, but to “sort out among the different types of vasculitis,” he said.
“It provides awareness and it provides a tool, especially for research investigation, but that seeps out into the broader community,” he added.
Dr. Merkel reported having no disclosures.
SOURCE: Merkel PA et al. ACR Annual Meeting, Presentation 5T116.
REPORTING FROM THE ACR ANNUAL MEETING
FFR by wire may soon be obsolete
SAN DIEGO – Angiograms can be deceiving, so it’s best to measure fractional flow reserve (FFR) across coronary obstructions to gauge patients’ true need for intervention. That’s hardly news to cardiologists, but FFR is not often done. The problem is that traditional measurement requires threading wires down coronary arteries; the technique is a bit risky and takes time and training. It also has to be repeated for each lesion.
But now, several companies are developing noninvasive ways to measure FFR.
Findings from one of them, CathWorks, were presented at the Transcatheter Cardiovascular Therapeutics annual meeting sponsored by the Cardiovascular Research Foundation. Its FFRangio system uses high-quality angiograms and an algorithm to estimate resistance and flow across stenoses. After a few cases, the process takes less than 5 minutes (Circulation. 2018 Sep 24. doi: 10.1161/CIRCULATIONAHA.118.037350).
“I think this is a big breakthrough. ... Ultimately, it should lead to better patient outcomes,” said lead investigator William Fearon, MD, professor of cardiology at Stanford University, Calif.
In an interview at TCT 2018, Dr. Fearon explained the importance of FFR, the data for FFRangio, and what’s coming down the pike from other companies. He disclosed institutional research grants from the company.
SAN DIEGO – Angiograms can be deceiving, so it’s best to measure fractional flow reserve (FFR) across coronary obstructions to gauge patients’ true need for intervention. That’s hardly news to cardiologists, but FFR is not often done. The problem is that traditional measurement requires threading wires down coronary arteries; the technique is a bit risky and takes time and training. It also has to be repeated for each lesion.
But now, several companies are developing noninvasive ways to measure FFR.
Findings from one of them, CathWorks, were presented at the Transcatheter Cardiovascular Therapeutics annual meeting sponsored by the Cardiovascular Research Foundation. Its FFRangio system uses high-quality angiograms and an algorithm to estimate resistance and flow across stenoses. After a few cases, the process takes less than 5 minutes (Circulation. 2018 Sep 24. doi: 10.1161/CIRCULATIONAHA.118.037350).
“I think this is a big breakthrough. ... Ultimately, it should lead to better patient outcomes,” said lead investigator William Fearon, MD, professor of cardiology at Stanford University, Calif.
In an interview at TCT 2018, Dr. Fearon explained the importance of FFR, the data for FFRangio, and what’s coming down the pike from other companies. He disclosed institutional research grants from the company.
SAN DIEGO – Angiograms can be deceiving, so it’s best to measure fractional flow reserve (FFR) across coronary obstructions to gauge patients’ true need for intervention. That’s hardly news to cardiologists, but FFR is not often done. The problem is that traditional measurement requires threading wires down coronary arteries; the technique is a bit risky and takes time and training. It also has to be repeated for each lesion.
But now, several companies are developing noninvasive ways to measure FFR.
Findings from one of them, CathWorks, were presented at the Transcatheter Cardiovascular Therapeutics annual meeting sponsored by the Cardiovascular Research Foundation. Its FFRangio system uses high-quality angiograms and an algorithm to estimate resistance and flow across stenoses. After a few cases, the process takes less than 5 minutes (Circulation. 2018 Sep 24. doi: 10.1161/CIRCULATIONAHA.118.037350).
“I think this is a big breakthrough. ... Ultimately, it should lead to better patient outcomes,” said lead investigator William Fearon, MD, professor of cardiology at Stanford University, Calif.
In an interview at TCT 2018, Dr. Fearon explained the importance of FFR, the data for FFRangio, and what’s coming down the pike from other companies. He disclosed institutional research grants from the company.
REPORTING FROM TCT 2018
Ablation plus transplant for severe scleroderma shows 11-year benefits
CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.
This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.
Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.
Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.
Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.
The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).
Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.
In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).
Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.
Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.
SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.
This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.
Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.
Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.
Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.
The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).
Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.
In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).
Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.
Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.
SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.
This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.
Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.
Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.
Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.
The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).
Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.
In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).
Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.
Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.
SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Survival after 11 years was 88% among transplanted patients and 53% among control patients treated with cyclophosphamide.
Study details: A long-term follow-up of 43 of the 75 patients enrolled in the SCOT trial.
Disclosures: SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
Source: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
High-dose flu vaccine in RA patients beats standard dose
CHICAGO – The administration of high-dose vs. standard-dose influenza vaccine provided substantially better immune responses in seropositive rheumatoid arthritis patients in a randomized, active-controlled trial.
High-dose trivalent influenza vaccine is known to improve immune responses in the elderly, but the current findings, which were presented at the annual meeting of the American College of Rheumatology, are the first to document a successful intervention to enhance vaccine responses in immunocompromised patients, according to Inés Colmegna, MD, of McGill University, Montreal.
Dr. Colmegna and her colleagues assessed antibody responses to either standard-dose (15 mcg of hemagglutinin per strain) quadrivalent inactivated influenza vaccine (SD-QIV) or high-dose (60 mcg of hemagglutinin per strain) trivalent inactivated influenza vaccine (HD-TIV) in 140 and 139 patients, respectively.
Seroprotection rates prior to vaccination were comparable in the two groups, but the high-dose recipients had consistently higher overall responses to vaccination.
Seroconversion rates were 22.3% vs. 8.6% (odds ratio, 2.93) for the H3N2 strain (A/HongKong/4801/2014), and 44.6% vs. 28.6% (OR, 1.93) for the B Victoria Lin strain (B/Brisbane/60/2008). For the H1N1 strain A/California/7/2009 in 2016-2017 and closely related A/Michigan/45/2015 in 2017-2018, the seroconversion rates were 51.1% vs. 30.0% (OR, 2.91) and 46.4% vs. 24.6% (OR, 2.79), respectively. Seroprotection rates for the H3N2 strain were 48.5% vs. 30.9%, and for the B Victoria Lin strain, 60.0% vs. 50.7%. The seroprotection rates for the H1N1 strains together were and 80.4% vs. 73.5%, Dr. Colmegna said.
Seroconversion was defined as at least a fourfold serum hemagglutination inhibition (HI) antibody increase from prevaccination level (day 0), and seroprotection was defined as percent with HI titers of 1:40 or greater at postvaccination day 28.
After the researchers controlled for age, vaccine type, treatment type in the 3 months prior to vaccination and during the study period, Charlson comorbidity index, and RA duration, the only significant predictors of vaccine seroresponse were vaccine dose and age.
The findings are notable because RA patients have a nearly threefold increase in the risk of contracting influenza infection or related illness, compared with age-matched healthy controls, because of “inherent immune dysfunction associated with RA, comorbidities, the age of our patients, and immunosuppressive therapy,” Dr. Colmegna said.
For this reason, RA patients are a priority group for annual vaccination. However, while vaccination remains the most effective method for preventing influenza and its associated complications, vaccine-induced antibody responses and protection in RA are suboptimal, she explained, noting that this puts them at increased risk for severe influenza.
“There is a high priority to develop new approaches to try to decrease this risk,” she said.
It was unknown whether HD-TIV – the only currently available high-dose influenza vaccine – would safely enhance antibody production in RA as it does in the elderly, so she and her colleagues recruited patients from a tertiary care center during the 2016-2017 and 2017-2018 Northern Hemisphere influenza seasons for this study.
The mean age of the patients was 61 years, and 80% were women. All were on stable treatment with either disease-modifying antirheumatic drugs (DMARDs) or biologics for at least 3 months prior to vaccination; treatment types included DMARDs in 138 patients (49.5%), anticytokine therapy in 92 patients (33%), and anti-B-cell therapy and small molecules in 49 patients (17.6%). An analysis by treatment type showed a possible reduction in the rate of seroconversion in patients who received anti-B-cell therapy and small molecules, but the number of patients in the group was too small to make definitive conclusions, Dr. Colmegna said.
Treatment in all groups was safe, with no differences in adverse events between those receiving high- or standard-dose vaccine, and none of the adverse events were related to treatment.
Further, the high-dose vaccine was not associated with an increase in disease activity.
“We believe that these results will likely change clinical practice,” she concluded.
Dr. Colmegna reported having no disclosures.
SOURCE: Colmegna I et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 837.
CHICAGO – The administration of high-dose vs. standard-dose influenza vaccine provided substantially better immune responses in seropositive rheumatoid arthritis patients in a randomized, active-controlled trial.
High-dose trivalent influenza vaccine is known to improve immune responses in the elderly, but the current findings, which were presented at the annual meeting of the American College of Rheumatology, are the first to document a successful intervention to enhance vaccine responses in immunocompromised patients, according to Inés Colmegna, MD, of McGill University, Montreal.
Dr. Colmegna and her colleagues assessed antibody responses to either standard-dose (15 mcg of hemagglutinin per strain) quadrivalent inactivated influenza vaccine (SD-QIV) or high-dose (60 mcg of hemagglutinin per strain) trivalent inactivated influenza vaccine (HD-TIV) in 140 and 139 patients, respectively.
Seroprotection rates prior to vaccination were comparable in the two groups, but the high-dose recipients had consistently higher overall responses to vaccination.
Seroconversion rates were 22.3% vs. 8.6% (odds ratio, 2.93) for the H3N2 strain (A/HongKong/4801/2014), and 44.6% vs. 28.6% (OR, 1.93) for the B Victoria Lin strain (B/Brisbane/60/2008). For the H1N1 strain A/California/7/2009 in 2016-2017 and closely related A/Michigan/45/2015 in 2017-2018, the seroconversion rates were 51.1% vs. 30.0% (OR, 2.91) and 46.4% vs. 24.6% (OR, 2.79), respectively. Seroprotection rates for the H3N2 strain were 48.5% vs. 30.9%, and for the B Victoria Lin strain, 60.0% vs. 50.7%. The seroprotection rates for the H1N1 strains together were and 80.4% vs. 73.5%, Dr. Colmegna said.
Seroconversion was defined as at least a fourfold serum hemagglutination inhibition (HI) antibody increase from prevaccination level (day 0), and seroprotection was defined as percent with HI titers of 1:40 or greater at postvaccination day 28.
After the researchers controlled for age, vaccine type, treatment type in the 3 months prior to vaccination and during the study period, Charlson comorbidity index, and RA duration, the only significant predictors of vaccine seroresponse were vaccine dose and age.
The findings are notable because RA patients have a nearly threefold increase in the risk of contracting influenza infection or related illness, compared with age-matched healthy controls, because of “inherent immune dysfunction associated with RA, comorbidities, the age of our patients, and immunosuppressive therapy,” Dr. Colmegna said.
For this reason, RA patients are a priority group for annual vaccination. However, while vaccination remains the most effective method for preventing influenza and its associated complications, vaccine-induced antibody responses and protection in RA are suboptimal, she explained, noting that this puts them at increased risk for severe influenza.
“There is a high priority to develop new approaches to try to decrease this risk,” she said.
It was unknown whether HD-TIV – the only currently available high-dose influenza vaccine – would safely enhance antibody production in RA as it does in the elderly, so she and her colleagues recruited patients from a tertiary care center during the 2016-2017 and 2017-2018 Northern Hemisphere influenza seasons for this study.
The mean age of the patients was 61 years, and 80% were women. All were on stable treatment with either disease-modifying antirheumatic drugs (DMARDs) or biologics for at least 3 months prior to vaccination; treatment types included DMARDs in 138 patients (49.5%), anticytokine therapy in 92 patients (33%), and anti-B-cell therapy and small molecules in 49 patients (17.6%). An analysis by treatment type showed a possible reduction in the rate of seroconversion in patients who received anti-B-cell therapy and small molecules, but the number of patients in the group was too small to make definitive conclusions, Dr. Colmegna said.
Treatment in all groups was safe, with no differences in adverse events between those receiving high- or standard-dose vaccine, and none of the adverse events were related to treatment.
Further, the high-dose vaccine was not associated with an increase in disease activity.
“We believe that these results will likely change clinical practice,” she concluded.
Dr. Colmegna reported having no disclosures.
SOURCE: Colmegna I et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 837.
CHICAGO – The administration of high-dose vs. standard-dose influenza vaccine provided substantially better immune responses in seropositive rheumatoid arthritis patients in a randomized, active-controlled trial.
High-dose trivalent influenza vaccine is known to improve immune responses in the elderly, but the current findings, which were presented at the annual meeting of the American College of Rheumatology, are the first to document a successful intervention to enhance vaccine responses in immunocompromised patients, according to Inés Colmegna, MD, of McGill University, Montreal.
Dr. Colmegna and her colleagues assessed antibody responses to either standard-dose (15 mcg of hemagglutinin per strain) quadrivalent inactivated influenza vaccine (SD-QIV) or high-dose (60 mcg of hemagglutinin per strain) trivalent inactivated influenza vaccine (HD-TIV) in 140 and 139 patients, respectively.
Seroprotection rates prior to vaccination were comparable in the two groups, but the high-dose recipients had consistently higher overall responses to vaccination.
Seroconversion rates were 22.3% vs. 8.6% (odds ratio, 2.93) for the H3N2 strain (A/HongKong/4801/2014), and 44.6% vs. 28.6% (OR, 1.93) for the B Victoria Lin strain (B/Brisbane/60/2008). For the H1N1 strain A/California/7/2009 in 2016-2017 and closely related A/Michigan/45/2015 in 2017-2018, the seroconversion rates were 51.1% vs. 30.0% (OR, 2.91) and 46.4% vs. 24.6% (OR, 2.79), respectively. Seroprotection rates for the H3N2 strain were 48.5% vs. 30.9%, and for the B Victoria Lin strain, 60.0% vs. 50.7%. The seroprotection rates for the H1N1 strains together were and 80.4% vs. 73.5%, Dr. Colmegna said.
Seroconversion was defined as at least a fourfold serum hemagglutination inhibition (HI) antibody increase from prevaccination level (day 0), and seroprotection was defined as percent with HI titers of 1:40 or greater at postvaccination day 28.
After the researchers controlled for age, vaccine type, treatment type in the 3 months prior to vaccination and during the study period, Charlson comorbidity index, and RA duration, the only significant predictors of vaccine seroresponse were vaccine dose and age.
The findings are notable because RA patients have a nearly threefold increase in the risk of contracting influenza infection or related illness, compared with age-matched healthy controls, because of “inherent immune dysfunction associated with RA, comorbidities, the age of our patients, and immunosuppressive therapy,” Dr. Colmegna said.
For this reason, RA patients are a priority group for annual vaccination. However, while vaccination remains the most effective method for preventing influenza and its associated complications, vaccine-induced antibody responses and protection in RA are suboptimal, she explained, noting that this puts them at increased risk for severe influenza.
“There is a high priority to develop new approaches to try to decrease this risk,” she said.
It was unknown whether HD-TIV – the only currently available high-dose influenza vaccine – would safely enhance antibody production in RA as it does in the elderly, so she and her colleagues recruited patients from a tertiary care center during the 2016-2017 and 2017-2018 Northern Hemisphere influenza seasons for this study.
The mean age of the patients was 61 years, and 80% were women. All were on stable treatment with either disease-modifying antirheumatic drugs (DMARDs) or biologics for at least 3 months prior to vaccination; treatment types included DMARDs in 138 patients (49.5%), anticytokine therapy in 92 patients (33%), and anti-B-cell therapy and small molecules in 49 patients (17.6%). An analysis by treatment type showed a possible reduction in the rate of seroconversion in patients who received anti-B-cell therapy and small molecules, but the number of patients in the group was too small to make definitive conclusions, Dr. Colmegna said.
Treatment in all groups was safe, with no differences in adverse events between those receiving high- or standard-dose vaccine, and none of the adverse events were related to treatment.
Further, the high-dose vaccine was not associated with an increase in disease activity.
“We believe that these results will likely change clinical practice,” she concluded.
Dr. Colmegna reported having no disclosures.
SOURCE: Colmegna I et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 837.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: High- vs. standard-dose flu vaccine improves immune responses in RA patients.
Major finding: High-dose trivalent inactivated influenza vaccine was associated with greater odds of H3N2, B Victoria Lin, and H1N1 seroconversion.
Study details: A randomized, active-controlled trial of 279 RA patients
Disclosures: Dr. Colmegna reported having no disclosures.
Source: Colmegna I et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 837.
Multiple interventions boost RA treat-to-target success
CHICAGO – A novel disease-management approach that paired routine monitoring of the clinical status of patients with RA and training for their rheumatologists on how to refine their treat-to-target practices led to a modest but meaningful boost in the achievement of treat-to-target goals in a single-center study with 2,549 patients.
After 1 year, patients assigned to the intervention program had a 12% improvement in their treat-to-target implementation score, compared with patients who received standard care, an increase that was “clinically meaningful,” Cianna L. Leatherwood, MD, said while presenting a poster at the annual meeting of the American College of Rheumatology.
This increased score represented improvements in its four components: measuring disease activity, using a disease activity score in treatment decision making, documenting evidence for creating a treatment goal, and making shared decisions, Dr. Leatherwood explained in a video interview. Some of Dr. Leatherwood’s collaborators in this study from Brigham and Women’s Hospital in Boston developed and first introduced the treat-to-target implementation score a few years ago (Arthritis Rheum. 2017 July;69[7]:1374-80).
The major interventions used in this program included having patients complete the Routine Assessment of Patient Index Data 3 index (Rheum Dis Clin North Am. 2009 Nov;35[4]:773-8) at every clinic encounter, focus-group discussions with panels of patients both prior to and during the year-long program, and monthly “learning collaborative sessions” for the nine rheumatologists in the intervention arm to discuss and develop treat-to-target practices, said Dr. Leatherwood, a rheumatologist at Kaiser Permanente in Oakland, Calif. The physicians in the intervention group also received frequent email reminders about adopting a treat-to-target approach. The control arm of the study included 11 rheumatologists who did not participate in these sessions or receive the reminders.
Dr. Leatherwood expressed confidence that other health systems could now adapt and use the treatment model she and her associates developed and tested after tailoring it to better match their local conditions.
The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
SOURCE: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
CHICAGO – A novel disease-management approach that paired routine monitoring of the clinical status of patients with RA and training for their rheumatologists on how to refine their treat-to-target practices led to a modest but meaningful boost in the achievement of treat-to-target goals in a single-center study with 2,549 patients.
After 1 year, patients assigned to the intervention program had a 12% improvement in their treat-to-target implementation score, compared with patients who received standard care, an increase that was “clinically meaningful,” Cianna L. Leatherwood, MD, said while presenting a poster at the annual meeting of the American College of Rheumatology.
This increased score represented improvements in its four components: measuring disease activity, using a disease activity score in treatment decision making, documenting evidence for creating a treatment goal, and making shared decisions, Dr. Leatherwood explained in a video interview. Some of Dr. Leatherwood’s collaborators in this study from Brigham and Women’s Hospital in Boston developed and first introduced the treat-to-target implementation score a few years ago (Arthritis Rheum. 2017 July;69[7]:1374-80).
The major interventions used in this program included having patients complete the Routine Assessment of Patient Index Data 3 index (Rheum Dis Clin North Am. 2009 Nov;35[4]:773-8) at every clinic encounter, focus-group discussions with panels of patients both prior to and during the year-long program, and monthly “learning collaborative sessions” for the nine rheumatologists in the intervention arm to discuss and develop treat-to-target practices, said Dr. Leatherwood, a rheumatologist at Kaiser Permanente in Oakland, Calif. The physicians in the intervention group also received frequent email reminders about adopting a treat-to-target approach. The control arm of the study included 11 rheumatologists who did not participate in these sessions or receive the reminders.
Dr. Leatherwood expressed confidence that other health systems could now adapt and use the treatment model she and her associates developed and tested after tailoring it to better match their local conditions.
The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
SOURCE: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
CHICAGO – A novel disease-management approach that paired routine monitoring of the clinical status of patients with RA and training for their rheumatologists on how to refine their treat-to-target practices led to a modest but meaningful boost in the achievement of treat-to-target goals in a single-center study with 2,549 patients.
After 1 year, patients assigned to the intervention program had a 12% improvement in their treat-to-target implementation score, compared with patients who received standard care, an increase that was “clinically meaningful,” Cianna L. Leatherwood, MD, said while presenting a poster at the annual meeting of the American College of Rheumatology.
This increased score represented improvements in its four components: measuring disease activity, using a disease activity score in treatment decision making, documenting evidence for creating a treatment goal, and making shared decisions, Dr. Leatherwood explained in a video interview. Some of Dr. Leatherwood’s collaborators in this study from Brigham and Women’s Hospital in Boston developed and first introduced the treat-to-target implementation score a few years ago (Arthritis Rheum. 2017 July;69[7]:1374-80).
The major interventions used in this program included having patients complete the Routine Assessment of Patient Index Data 3 index (Rheum Dis Clin North Am. 2009 Nov;35[4]:773-8) at every clinic encounter, focus-group discussions with panels of patients both prior to and during the year-long program, and monthly “learning collaborative sessions” for the nine rheumatologists in the intervention arm to discuss and develop treat-to-target practices, said Dr. Leatherwood, a rheumatologist at Kaiser Permanente in Oakland, Calif. The physicians in the intervention group also received frequent email reminders about adopting a treat-to-target approach. The control arm of the study included 11 rheumatologists who did not participate in these sessions or receive the reminders.
Dr. Leatherwood expressed confidence that other health systems could now adapt and use the treatment model she and her associates developed and tested after tailoring it to better match their local conditions.
The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
SOURCE: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: After 1 year, the treat-to-target implementation score in the intervention patients was 12% higher than among the control patients.
Study details: A single-center, controlled study with 2,549 RA patients and 22 rheumatologists.
Disclosures: The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
Source: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
