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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
Isradipine for Parkinson’s disease fails in phase 3 study
PHILADELPHIA - There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.
Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.
“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.
Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.
The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.
The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.
Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.
These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.
Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.
The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.
PHILADELPHIA - There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.
Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.
“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.
Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.
The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.
The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.
Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.
These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.
Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.
The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.
PHILADELPHIA - There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.
Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.
“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.
Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.
The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.
The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.
Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.
These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.
Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.
The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.
FROM AAN 2019
Increase in pediatric thyroid cancers: overdiagnosis or something more?
Thyroid cancer rates are on the rise in U.S. pediatric patients, a large epidemiologic study shows, and researchers say the trend can’t be explained away purely as overdiagnosis.
However, the extent of a real increase in clinically significant cancers and what might be causing that increase remains unclear, according to authors of the study and two related editorials appearing in the journal Cancer.
Cases of pediatric differentiated thyroid cancer (DTC) cases increased by 4.43% per year in the study, which was based on data from 39 U.S. cancer registries. Increases were seen in both smaller early-stage and larger late-stage tumors, leading study authors to assert that the trend was “unlikely to be explained solely by increased medical surveillance or improved detection.”
“Environmental and individual factors may also have affected rising trends,” said Meredith S. Shiels, PhD, of the National Cancer Institute and coauthors in a report on the study.
A true increase in pediatric thyroid cancer incidence is a possibility, authors of a related editorial said; however, they also expressed concern that inferences drawn from this U.S. cancer epidemiology data may be “artifactual.”
“We believe that first it is most important to closely examine the reasons for the increase that could be attributable to overdiagnosis, given this appears to be a likely explanation,” said authors of one editorial, including Amy Y. Chen, MD, MPH, of Emory University, Atlanta, and Louise Davies, MD, MS, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.
Overdiagnosis does occur, but the “real component” of the rise in thyroid cancer incidence cannot be ignored, according to a second editorial by David Goldenberg, MD, of Penn State University, Hershey.
“Although many authors are quick to explain the rise in thyroid cancer as an artifact of the overdiagnosis of clinically insignificant thyroid cancers, multiple groups all over the world have shown that this is not sufficient to explain the rise in thyroid cancer,” Dr. Goldenberg said in his editorial.
New data in pediatric patients
Pediatric DTCs are rare, representing just 2%-4% of pediatric malignancies, and they’re particularly rare in relation to adult cases, comprising about 2.3% of thyroid cancer diagnoses overall, according to Dr. Shiels and coauthors of the current study.
“The rarity of pediatric DTC, the lack of information on histologic features, or both have prevented prior studies from analyzing trends by tumor size or cancer stage at diagnosis,” they said.
To address this knowledge gap, Dr. Shiels and colleagues analyzed a total of 7,296 primary DTCs in children aged 0-19 years in data obtained from the North American Association of Central Cancer Registries. Ninety-one percent of these pediatric patients had papillary thyroid cancer, 83% were female, and 76% were between the ages of 15 to 19 years.
The rate of pediatric DTCs increased from 4.77 per million in 1998 to 8.82 per million in 2013, representing an increase of 4.43% per year, they found.
Both localized and more aggressive tumors increased in incidence over that time period, they also found. The annual increase was 4.06% for local stage at diagnosis, 5.68% for regional, and 8.55% for distant disease.
Similarly, increases were seen in small and large tumors alike. The annual percentage increase was 9.46% for tumors smaller than 1 cm, and 4.69% for tumors greater than 2 cm, according to the report.
Looking at age, investigators found that the increases in incidence were significant only for 10- to 19-year-olds, while significant increases were consistently observed for both sexes and for all races and ethnicities.
Overdiagnosis vs. environmental factors and lifestyle changes
If further investigations point to detection of subclinical disease as the cause of the increases in pediatric DTC incidence then initiatives may be needed to curtail use of CT scans, ultrasound, and needle biopsies, as has been done in adults, Dr. Chen and Dr. Davies said in their editorial.
“When the American Thyroid Association modified their guidelines for needle biopsy of nodules to discourage sampling of small lesions, a corresponding decrease in incidence rates was observed, suggesting that, indeed, overdiagnosis was the culprit,” they said.
Although it’s not clear what environmental factors or lifestyle changes are driving an increase, obesity has been consistently linked to increases in thyroid cancer, Dr. Goldenberg said. Conversely, smoking has been linked to reduced thyroid cancer risk, which means reduced prevalence of smoking in the community could potentially contribute to increased thyroid cancer incidence.
“It is our role as physicians to protect our patients from complacency and undertreatment,” he concluded in his editorial. “Explaining away thyroid cancers as being subclinical or clinically insignificant is reminiscent of days past when we told our patients: ‘Don’t worry, it’s good cancer.’ ”
The research by Dr. Shiels and colleagues was supported by the Intramural Research Program of the National Cancer Institute. Dr. Shiels and coauthors made no conflict of interest disclosures related to their report.
SOURCE: Shiels MO et al. Cancer. 2019 Apr 23. doi: 10.1002/cncr.32125.
Thyroid cancer rates are on the rise in U.S. pediatric patients, a large epidemiologic study shows, and researchers say the trend can’t be explained away purely as overdiagnosis.
However, the extent of a real increase in clinically significant cancers and what might be causing that increase remains unclear, according to authors of the study and two related editorials appearing in the journal Cancer.
Cases of pediatric differentiated thyroid cancer (DTC) cases increased by 4.43% per year in the study, which was based on data from 39 U.S. cancer registries. Increases were seen in both smaller early-stage and larger late-stage tumors, leading study authors to assert that the trend was “unlikely to be explained solely by increased medical surveillance or improved detection.”
“Environmental and individual factors may also have affected rising trends,” said Meredith S. Shiels, PhD, of the National Cancer Institute and coauthors in a report on the study.
A true increase in pediatric thyroid cancer incidence is a possibility, authors of a related editorial said; however, they also expressed concern that inferences drawn from this U.S. cancer epidemiology data may be “artifactual.”
“We believe that first it is most important to closely examine the reasons for the increase that could be attributable to overdiagnosis, given this appears to be a likely explanation,” said authors of one editorial, including Amy Y. Chen, MD, MPH, of Emory University, Atlanta, and Louise Davies, MD, MS, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.
Overdiagnosis does occur, but the “real component” of the rise in thyroid cancer incidence cannot be ignored, according to a second editorial by David Goldenberg, MD, of Penn State University, Hershey.
“Although many authors are quick to explain the rise in thyroid cancer as an artifact of the overdiagnosis of clinically insignificant thyroid cancers, multiple groups all over the world have shown that this is not sufficient to explain the rise in thyroid cancer,” Dr. Goldenberg said in his editorial.
New data in pediatric patients
Pediatric DTCs are rare, representing just 2%-4% of pediatric malignancies, and they’re particularly rare in relation to adult cases, comprising about 2.3% of thyroid cancer diagnoses overall, according to Dr. Shiels and coauthors of the current study.
“The rarity of pediatric DTC, the lack of information on histologic features, or both have prevented prior studies from analyzing trends by tumor size or cancer stage at diagnosis,” they said.
To address this knowledge gap, Dr. Shiels and colleagues analyzed a total of 7,296 primary DTCs in children aged 0-19 years in data obtained from the North American Association of Central Cancer Registries. Ninety-one percent of these pediatric patients had papillary thyroid cancer, 83% were female, and 76% were between the ages of 15 to 19 years.
The rate of pediatric DTCs increased from 4.77 per million in 1998 to 8.82 per million in 2013, representing an increase of 4.43% per year, they found.
Both localized and more aggressive tumors increased in incidence over that time period, they also found. The annual increase was 4.06% for local stage at diagnosis, 5.68% for regional, and 8.55% for distant disease.
Similarly, increases were seen in small and large tumors alike. The annual percentage increase was 9.46% for tumors smaller than 1 cm, and 4.69% for tumors greater than 2 cm, according to the report.
Looking at age, investigators found that the increases in incidence were significant only for 10- to 19-year-olds, while significant increases were consistently observed for both sexes and for all races and ethnicities.
Overdiagnosis vs. environmental factors and lifestyle changes
If further investigations point to detection of subclinical disease as the cause of the increases in pediatric DTC incidence then initiatives may be needed to curtail use of CT scans, ultrasound, and needle biopsies, as has been done in adults, Dr. Chen and Dr. Davies said in their editorial.
“When the American Thyroid Association modified their guidelines for needle biopsy of nodules to discourage sampling of small lesions, a corresponding decrease in incidence rates was observed, suggesting that, indeed, overdiagnosis was the culprit,” they said.
Although it’s not clear what environmental factors or lifestyle changes are driving an increase, obesity has been consistently linked to increases in thyroid cancer, Dr. Goldenberg said. Conversely, smoking has been linked to reduced thyroid cancer risk, which means reduced prevalence of smoking in the community could potentially contribute to increased thyroid cancer incidence.
“It is our role as physicians to protect our patients from complacency and undertreatment,” he concluded in his editorial. “Explaining away thyroid cancers as being subclinical or clinically insignificant is reminiscent of days past when we told our patients: ‘Don’t worry, it’s good cancer.’ ”
The research by Dr. Shiels and colleagues was supported by the Intramural Research Program of the National Cancer Institute. Dr. Shiels and coauthors made no conflict of interest disclosures related to their report.
SOURCE: Shiels MO et al. Cancer. 2019 Apr 23. doi: 10.1002/cncr.32125.
Thyroid cancer rates are on the rise in U.S. pediatric patients, a large epidemiologic study shows, and researchers say the trend can’t be explained away purely as overdiagnosis.
However, the extent of a real increase in clinically significant cancers and what might be causing that increase remains unclear, according to authors of the study and two related editorials appearing in the journal Cancer.
Cases of pediatric differentiated thyroid cancer (DTC) cases increased by 4.43% per year in the study, which was based on data from 39 U.S. cancer registries. Increases were seen in both smaller early-stage and larger late-stage tumors, leading study authors to assert that the trend was “unlikely to be explained solely by increased medical surveillance or improved detection.”
“Environmental and individual factors may also have affected rising trends,” said Meredith S. Shiels, PhD, of the National Cancer Institute and coauthors in a report on the study.
A true increase in pediatric thyroid cancer incidence is a possibility, authors of a related editorial said; however, they also expressed concern that inferences drawn from this U.S. cancer epidemiology data may be “artifactual.”
“We believe that first it is most important to closely examine the reasons for the increase that could be attributable to overdiagnosis, given this appears to be a likely explanation,” said authors of one editorial, including Amy Y. Chen, MD, MPH, of Emory University, Atlanta, and Louise Davies, MD, MS, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.
Overdiagnosis does occur, but the “real component” of the rise in thyroid cancer incidence cannot be ignored, according to a second editorial by David Goldenberg, MD, of Penn State University, Hershey.
“Although many authors are quick to explain the rise in thyroid cancer as an artifact of the overdiagnosis of clinically insignificant thyroid cancers, multiple groups all over the world have shown that this is not sufficient to explain the rise in thyroid cancer,” Dr. Goldenberg said in his editorial.
New data in pediatric patients
Pediatric DTCs are rare, representing just 2%-4% of pediatric malignancies, and they’re particularly rare in relation to adult cases, comprising about 2.3% of thyroid cancer diagnoses overall, according to Dr. Shiels and coauthors of the current study.
“The rarity of pediatric DTC, the lack of information on histologic features, or both have prevented prior studies from analyzing trends by tumor size or cancer stage at diagnosis,” they said.
To address this knowledge gap, Dr. Shiels and colleagues analyzed a total of 7,296 primary DTCs in children aged 0-19 years in data obtained from the North American Association of Central Cancer Registries. Ninety-one percent of these pediatric patients had papillary thyroid cancer, 83% were female, and 76% were between the ages of 15 to 19 years.
The rate of pediatric DTCs increased from 4.77 per million in 1998 to 8.82 per million in 2013, representing an increase of 4.43% per year, they found.
Both localized and more aggressive tumors increased in incidence over that time period, they also found. The annual increase was 4.06% for local stage at diagnosis, 5.68% for regional, and 8.55% for distant disease.
Similarly, increases were seen in small and large tumors alike. The annual percentage increase was 9.46% for tumors smaller than 1 cm, and 4.69% for tumors greater than 2 cm, according to the report.
Looking at age, investigators found that the increases in incidence were significant only for 10- to 19-year-olds, while significant increases were consistently observed for both sexes and for all races and ethnicities.
Overdiagnosis vs. environmental factors and lifestyle changes
If further investigations point to detection of subclinical disease as the cause of the increases in pediatric DTC incidence then initiatives may be needed to curtail use of CT scans, ultrasound, and needle biopsies, as has been done in adults, Dr. Chen and Dr. Davies said in their editorial.
“When the American Thyroid Association modified their guidelines for needle biopsy of nodules to discourage sampling of small lesions, a corresponding decrease in incidence rates was observed, suggesting that, indeed, overdiagnosis was the culprit,” they said.
Although it’s not clear what environmental factors or lifestyle changes are driving an increase, obesity has been consistently linked to increases in thyroid cancer, Dr. Goldenberg said. Conversely, smoking has been linked to reduced thyroid cancer risk, which means reduced prevalence of smoking in the community could potentially contribute to increased thyroid cancer incidence.
“It is our role as physicians to protect our patients from complacency and undertreatment,” he concluded in his editorial. “Explaining away thyroid cancers as being subclinical or clinically insignificant is reminiscent of days past when we told our patients: ‘Don’t worry, it’s good cancer.’ ”
The research by Dr. Shiels and colleagues was supported by the Intramural Research Program of the National Cancer Institute. Dr. Shiels and coauthors made no conflict of interest disclosures related to their report.
SOURCE: Shiels MO et al. Cancer. 2019 Apr 23. doi: 10.1002/cncr.32125.
FROM CANCER
Opicapone increased on-time without dyskinesia in patients with Parkinson’s disease
PHILADELPHIA -
The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.
“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”
Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.
The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.
In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).
The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.
In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.
Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.
Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.
Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.
SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.
PHILADELPHIA -
The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.
“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”
Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.
The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.
In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).
The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.
In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.
Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.
Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.
Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.
SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.
PHILADELPHIA -
The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.
“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”
Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.
The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.
In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).
The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.
In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.
Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.
Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.
Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.
SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.
FROM AAN 2019
PsA patients had durable responses after 1 year of IV golimumab treatment
, according to follow-up results of a randomized clinical trial.
The improvements in joint disease, skin disease, and health-related quality of life seen at 24 weeks in the phase 3 GO-VIBRANT study were maintained at this 52-week follow-up, according to M. Elaine Husni, MD, of the Cleveland Clinic, and coinvestigators.
Patients who crossed over to golimumab treatment after 24 weeks of placebo had similar rates of clinical response at 52 weeks, while patients receiving concomitant methotrexate had similar ACR response rates, compared with patients on golimumab monotherapy, Dr. Husni and colleagues reported.
Many patients who were not ACR20 responders at week 52 nevertheless had improvements in skin disease, enthesitis, and dactylitis, an exploratory analysis showed.
“These factors may have contributed to these patients remaining in the trial and continuing golimumab therapy despite not achieving an ACR20 response,” wrote Dr. Husni and coauthors. The report is in Arthritis Care & Research.
The Food and Drug Administration approved a once-monthly subcutaneous formulation of golimumab (Simponi) in 2009 for treatment of moderate to severe active psoriatic arthritis, rheumatoid arthritis, and active ankylosing spondylitis. The intravenous formulation of this TNF inhibitor (Simponi Aria) received a psoriatic arthritis indication in 2017 based on GO-VIBRANT data. Published results at the time showed that compared with placebo, intravenous golimumab given as a 2-mg/kg infusion at weeks 0, 4, and then every 8 weeks produced greater improvements in psoriatic arthritis signs and symptoms and less radiographic progression through week 24 of the study, and had adverse events consistent with other TNF inhibitors, according to investigators.
The follow-up report includes efficacy and safety data for golimumab-treated patients beyond 24 weeks, as well as data for patients on the placebo arm, who crossed over to receive golimumab at week 24, week 28, and then every 8 weeks thereafter.
The results show ACR response rates were maintained from week 24 to 52 in golimumab-treated patients, and were similar in the placebo crossover patients. The ACR20, ACR50, and ACR70 response rates in the golimumab group were 76.8%, 58.1%, and 38.6%, respectively, while in the crossover group, they were 77.0%, 53.6%, and 33.9%, respectively.
Radiographic progression was measured using van der Heijde-Sharp (vdH-S) score with modifications for psoriatic arthritis. The mean change in vdH-S score at 24 weeks was –0.4 and 2.0 in the golimumab and placebo groups, respectively; by week 52, the mean change was –0.5 and 0.8 for golimumab and placebo crossover.
Infection was the most common adverse event throughout 60 weeks of safety evaluation, occurring in 22.8% of all golimumab-treated patients, investigators said. Four infusion reactions occurred following golimumab administration, though none were considered serious or severe.
The GO-VIBRANT study, which comprised 480 adults, had limited follow-up and was not powered to identify rare safety events, investigators said.
“However, the totality of results through 1 year of the GO-VIBRANT study show a durable response to IV golimumab 2 mg/kg across several clinical efficacy, HRQoL, and radiographic endpoints with no new safety signals,” they concluded.
Study authors reported disclosures with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Sanofi, and UCB. Several study authors reported current or former employment with Janssen Research & Development and stock or stock options in Johnson & Johnson.
SOURCE: Husni ME et al. Arthritis Care Res. 2019 Apr 12. doi: 10.1002/acr.23905.
, according to follow-up results of a randomized clinical trial.
The improvements in joint disease, skin disease, and health-related quality of life seen at 24 weeks in the phase 3 GO-VIBRANT study were maintained at this 52-week follow-up, according to M. Elaine Husni, MD, of the Cleveland Clinic, and coinvestigators.
Patients who crossed over to golimumab treatment after 24 weeks of placebo had similar rates of clinical response at 52 weeks, while patients receiving concomitant methotrexate had similar ACR response rates, compared with patients on golimumab monotherapy, Dr. Husni and colleagues reported.
Many patients who were not ACR20 responders at week 52 nevertheless had improvements in skin disease, enthesitis, and dactylitis, an exploratory analysis showed.
“These factors may have contributed to these patients remaining in the trial and continuing golimumab therapy despite not achieving an ACR20 response,” wrote Dr. Husni and coauthors. The report is in Arthritis Care & Research.
The Food and Drug Administration approved a once-monthly subcutaneous formulation of golimumab (Simponi) in 2009 for treatment of moderate to severe active psoriatic arthritis, rheumatoid arthritis, and active ankylosing spondylitis. The intravenous formulation of this TNF inhibitor (Simponi Aria) received a psoriatic arthritis indication in 2017 based on GO-VIBRANT data. Published results at the time showed that compared with placebo, intravenous golimumab given as a 2-mg/kg infusion at weeks 0, 4, and then every 8 weeks produced greater improvements in psoriatic arthritis signs and symptoms and less radiographic progression through week 24 of the study, and had adverse events consistent with other TNF inhibitors, according to investigators.
The follow-up report includes efficacy and safety data for golimumab-treated patients beyond 24 weeks, as well as data for patients on the placebo arm, who crossed over to receive golimumab at week 24, week 28, and then every 8 weeks thereafter.
The results show ACR response rates were maintained from week 24 to 52 in golimumab-treated patients, and were similar in the placebo crossover patients. The ACR20, ACR50, and ACR70 response rates in the golimumab group were 76.8%, 58.1%, and 38.6%, respectively, while in the crossover group, they were 77.0%, 53.6%, and 33.9%, respectively.
Radiographic progression was measured using van der Heijde-Sharp (vdH-S) score with modifications for psoriatic arthritis. The mean change in vdH-S score at 24 weeks was –0.4 and 2.0 in the golimumab and placebo groups, respectively; by week 52, the mean change was –0.5 and 0.8 for golimumab and placebo crossover.
Infection was the most common adverse event throughout 60 weeks of safety evaluation, occurring in 22.8% of all golimumab-treated patients, investigators said. Four infusion reactions occurred following golimumab administration, though none were considered serious or severe.
The GO-VIBRANT study, which comprised 480 adults, had limited follow-up and was not powered to identify rare safety events, investigators said.
“However, the totality of results through 1 year of the GO-VIBRANT study show a durable response to IV golimumab 2 mg/kg across several clinical efficacy, HRQoL, and radiographic endpoints with no new safety signals,” they concluded.
Study authors reported disclosures with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Sanofi, and UCB. Several study authors reported current or former employment with Janssen Research & Development and stock or stock options in Johnson & Johnson.
SOURCE: Husni ME et al. Arthritis Care Res. 2019 Apr 12. doi: 10.1002/acr.23905.
, according to follow-up results of a randomized clinical trial.
The improvements in joint disease, skin disease, and health-related quality of life seen at 24 weeks in the phase 3 GO-VIBRANT study were maintained at this 52-week follow-up, according to M. Elaine Husni, MD, of the Cleveland Clinic, and coinvestigators.
Patients who crossed over to golimumab treatment after 24 weeks of placebo had similar rates of clinical response at 52 weeks, while patients receiving concomitant methotrexate had similar ACR response rates, compared with patients on golimumab monotherapy, Dr. Husni and colleagues reported.
Many patients who were not ACR20 responders at week 52 nevertheless had improvements in skin disease, enthesitis, and dactylitis, an exploratory analysis showed.
“These factors may have contributed to these patients remaining in the trial and continuing golimumab therapy despite not achieving an ACR20 response,” wrote Dr. Husni and coauthors. The report is in Arthritis Care & Research.
The Food and Drug Administration approved a once-monthly subcutaneous formulation of golimumab (Simponi) in 2009 for treatment of moderate to severe active psoriatic arthritis, rheumatoid arthritis, and active ankylosing spondylitis. The intravenous formulation of this TNF inhibitor (Simponi Aria) received a psoriatic arthritis indication in 2017 based on GO-VIBRANT data. Published results at the time showed that compared with placebo, intravenous golimumab given as a 2-mg/kg infusion at weeks 0, 4, and then every 8 weeks produced greater improvements in psoriatic arthritis signs and symptoms and less radiographic progression through week 24 of the study, and had adverse events consistent with other TNF inhibitors, according to investigators.
The follow-up report includes efficacy and safety data for golimumab-treated patients beyond 24 weeks, as well as data for patients on the placebo arm, who crossed over to receive golimumab at week 24, week 28, and then every 8 weeks thereafter.
The results show ACR response rates were maintained from week 24 to 52 in golimumab-treated patients, and were similar in the placebo crossover patients. The ACR20, ACR50, and ACR70 response rates in the golimumab group were 76.8%, 58.1%, and 38.6%, respectively, while in the crossover group, they were 77.0%, 53.6%, and 33.9%, respectively.
Radiographic progression was measured using van der Heijde-Sharp (vdH-S) score with modifications for psoriatic arthritis. The mean change in vdH-S score at 24 weeks was –0.4 and 2.0 in the golimumab and placebo groups, respectively; by week 52, the mean change was –0.5 and 0.8 for golimumab and placebo crossover.
Infection was the most common adverse event throughout 60 weeks of safety evaluation, occurring in 22.8% of all golimumab-treated patients, investigators said. Four infusion reactions occurred following golimumab administration, though none were considered serious or severe.
The GO-VIBRANT study, which comprised 480 adults, had limited follow-up and was not powered to identify rare safety events, investigators said.
“However, the totality of results through 1 year of the GO-VIBRANT study show a durable response to IV golimumab 2 mg/kg across several clinical efficacy, HRQoL, and radiographic endpoints with no new safety signals,” they concluded.
Study authors reported disclosures with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Sanofi, and UCB. Several study authors reported current or former employment with Janssen Research & Development and stock or stock options in Johnson & Johnson.
SOURCE: Husni ME et al. Arthritis Care Res. 2019 Apr 12. doi: 10.1002/acr.23905.
FROM ARTHRITIS CARE & RESEARCH
Patients say primary care video visits are convenient, high quality
Most patients thought video visits integrated into their existing primary care practice were convenient, provided high-quality care, and strengthened their relationship with their provider, results of a recent survey show.
The video calls may reduce in-person primary care visits, particularly for the two-thirds of patients who otherwise would need to take off from work or make other arrangements to visit the office, according to researcher Mary E. Reed, DrPH, of the Kaiser Permanente Division of Research, Oakland, Calif., and coauthors.*
“Integrated video telemedicine may be a transformative tool in increasing patient-centered access to health care,” the researcher noted in a report on the survey in the Annals of Internal Medicine.
Millions of patients have used direct-to-consumer telemedicine services that are not necessarily integrated with the patient’s electronic medical records and may not provide access to the providers they are accustomed to seeing, investigators said in their report.
By contrast, “house call” video visits that were integrated into existing primary care practices may provide convenience plus access to patients’ usual providers. However, there’s only limited evidence on the patient experience with such integrations, they said.
To fill that information gap, Dr. Reed and colleagues surveyed adults with a scheduled video telemedicine visit with a primary care provider in Kaiser Permanente Northern California. A total of 1,274 patients provided responses.
The Kaiser Permanente telemedicine system allows all primary care providers to have video visits with patients. “Through Internet-connected and video-enabled computers or mobile devices, patients can join video visits from anywhere, and available clinicians include their own providers,” the researchers said in their report.
Of the patients surveyed, 87% said they scheduled a video visit because it was more convenient than other ways of receiving care. Furthermore, 93% said their video visit adequately addressed their needs, 90% said they were confident in the quality of care, and 84% agreed that the ability to have a video visit strengthened their relationship with the provider.
Of the patients who participated in the study, 67% said that, if the visit had been in person, they would have needed to have made at least one arrangement; time off from work was the issue for more than half of participants, though many cited childcare, coverage for another activity or responsibility, or arrangements with someone else to accompany them to the visit as issues.
Concerns with video visits were reported by some patients, researchers said. Twenty-one percent said they were worried that treatment would not be adequate, and 11% said they were concerned about the privacy of medical information.
Moreover, 41% of patients who had scheduled video visits said they preferred to get care in person, the survey results show.
Even so, 89% of patients said they were interested in a future video visit, according to the researchers.
Dr. Reed and coauthors declared no conflicts of interest related to this research, which was supported by a grant from Kaiser Permanente Division of Research.
SOURCE: Reed ME et al. Ann Intern Med. 2019 Apr 29. doi: 10.7326/M18-3081.
*Correction, 4/30/19: An earlier version of this article misstated the location of the Kaiser Permanente Division of Research.
Most patients thought video visits integrated into their existing primary care practice were convenient, provided high-quality care, and strengthened their relationship with their provider, results of a recent survey show.
The video calls may reduce in-person primary care visits, particularly for the two-thirds of patients who otherwise would need to take off from work or make other arrangements to visit the office, according to researcher Mary E. Reed, DrPH, of the Kaiser Permanente Division of Research, Oakland, Calif., and coauthors.*
“Integrated video telemedicine may be a transformative tool in increasing patient-centered access to health care,” the researcher noted in a report on the survey in the Annals of Internal Medicine.
Millions of patients have used direct-to-consumer telemedicine services that are not necessarily integrated with the patient’s electronic medical records and may not provide access to the providers they are accustomed to seeing, investigators said in their report.
By contrast, “house call” video visits that were integrated into existing primary care practices may provide convenience plus access to patients’ usual providers. However, there’s only limited evidence on the patient experience with such integrations, they said.
To fill that information gap, Dr. Reed and colleagues surveyed adults with a scheduled video telemedicine visit with a primary care provider in Kaiser Permanente Northern California. A total of 1,274 patients provided responses.
The Kaiser Permanente telemedicine system allows all primary care providers to have video visits with patients. “Through Internet-connected and video-enabled computers or mobile devices, patients can join video visits from anywhere, and available clinicians include their own providers,” the researchers said in their report.
Of the patients surveyed, 87% said they scheduled a video visit because it was more convenient than other ways of receiving care. Furthermore, 93% said their video visit adequately addressed their needs, 90% said they were confident in the quality of care, and 84% agreed that the ability to have a video visit strengthened their relationship with the provider.
Of the patients who participated in the study, 67% said that, if the visit had been in person, they would have needed to have made at least one arrangement; time off from work was the issue for more than half of participants, though many cited childcare, coverage for another activity or responsibility, or arrangements with someone else to accompany them to the visit as issues.
Concerns with video visits were reported by some patients, researchers said. Twenty-one percent said they were worried that treatment would not be adequate, and 11% said they were concerned about the privacy of medical information.
Moreover, 41% of patients who had scheduled video visits said they preferred to get care in person, the survey results show.
Even so, 89% of patients said they were interested in a future video visit, according to the researchers.
Dr. Reed and coauthors declared no conflicts of interest related to this research, which was supported by a grant from Kaiser Permanente Division of Research.
SOURCE: Reed ME et al. Ann Intern Med. 2019 Apr 29. doi: 10.7326/M18-3081.
*Correction, 4/30/19: An earlier version of this article misstated the location of the Kaiser Permanente Division of Research.
Most patients thought video visits integrated into their existing primary care practice were convenient, provided high-quality care, and strengthened their relationship with their provider, results of a recent survey show.
The video calls may reduce in-person primary care visits, particularly for the two-thirds of patients who otherwise would need to take off from work or make other arrangements to visit the office, according to researcher Mary E. Reed, DrPH, of the Kaiser Permanente Division of Research, Oakland, Calif., and coauthors.*
“Integrated video telemedicine may be a transformative tool in increasing patient-centered access to health care,” the researcher noted in a report on the survey in the Annals of Internal Medicine.
Millions of patients have used direct-to-consumer telemedicine services that are not necessarily integrated with the patient’s electronic medical records and may not provide access to the providers they are accustomed to seeing, investigators said in their report.
By contrast, “house call” video visits that were integrated into existing primary care practices may provide convenience plus access to patients’ usual providers. However, there’s only limited evidence on the patient experience with such integrations, they said.
To fill that information gap, Dr. Reed and colleagues surveyed adults with a scheduled video telemedicine visit with a primary care provider in Kaiser Permanente Northern California. A total of 1,274 patients provided responses.
The Kaiser Permanente telemedicine system allows all primary care providers to have video visits with patients. “Through Internet-connected and video-enabled computers or mobile devices, patients can join video visits from anywhere, and available clinicians include their own providers,” the researchers said in their report.
Of the patients surveyed, 87% said they scheduled a video visit because it was more convenient than other ways of receiving care. Furthermore, 93% said their video visit adequately addressed their needs, 90% said they were confident in the quality of care, and 84% agreed that the ability to have a video visit strengthened their relationship with the provider.
Of the patients who participated in the study, 67% said that, if the visit had been in person, they would have needed to have made at least one arrangement; time off from work was the issue for more than half of participants, though many cited childcare, coverage for another activity or responsibility, or arrangements with someone else to accompany them to the visit as issues.
Concerns with video visits were reported by some patients, researchers said. Twenty-one percent said they were worried that treatment would not be adequate, and 11% said they were concerned about the privacy of medical information.
Moreover, 41% of patients who had scheduled video visits said they preferred to get care in person, the survey results show.
Even so, 89% of patients said they were interested in a future video visit, according to the researchers.
Dr. Reed and coauthors declared no conflicts of interest related to this research, which was supported by a grant from Kaiser Permanente Division of Research.
SOURCE: Reed ME et al. Ann Intern Med. 2019 Apr 29. doi: 10.7326/M18-3081.
*Correction, 4/30/19: An earlier version of this article misstated the location of the Kaiser Permanente Division of Research.
FROM THE ANNALS OF INTERNAL MEDICINE
Key clinical point:
Major finding: Of patients surveyed, 93% said their video visit adequately addressed their needs, 90% were confident in the quality of care, and 84% said it strengthened their relationship with the provider.
Study details: Survey responses from 1,274 adults with a scheduled video telemedicine visit with a primary care provider in Kaiser Permanente Northern California.
Disclosures: The authors declared no conflicts of interest related to this work, which was supported by a grant from the Kaiser Permanente Division of Research.
Source: Reed ME et al. Ann Intern Med. 2019 Apr 29. doi: 10.7326/M18-3081.
Head and neck cancer cost analysis yields simple bundled payment model
While many factors can influence cost in head and neck cancer, a simple bundled payments model for the disease can be developed based solely on treatment types, researchers reported.
The number of treatment modalities was the biggest driver of cost in an analysis of 150 head and neck cancer patients. Whether those patients needed single-modality, bimodality, or trimodality treatment was in turn driven by the stage of the disease; by contrast, patient factors had no significant cost impacts, the investigators found.
Based on those findings, they developed a three-tiered cost model in which surgery or radiation was the least costly, chemoradiation or surgery plus radiation was next, and surgery plus chemoradiation was associated with the highest cost.
Basing bundled payments on treatment modality is a “simple but clinically robust model” for payment selection in head and neck cancer patients, wrote senior author Matthew C. Ward, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., and coauthors.
“A tiered system driven by treatment complexity will aid providers who seek to stratify financial risk in a simple and meaningful manner,” Dr. Ward and colleagues wrote in the Journal of Oncology Practice.
As cancer costs rise, bundled payment models seek to “incentivize value and reduce administrative waste” with a single payment per episode of care, shared by all providers contributing to that episode, they wrote. However, there have been few cancer-specific bundled payment programs described to date.
The tiered approach was based on an analysis of 150 patients with stage 0 to IVB head and neck cancer, excluding those with recurrent or metastatic disease and those treated with palliative intent. Most (58%) had stage IVA disease and the oropharynx was the tumor subsite in 48%.
Direct costs could not be published because of institutional policy, according to Dr. Ward and coauthors, who instead reported overall costs of treatment as relative median costs, or the ratio of the cost of a specific treatment versus the cost of surgery alone.
Specifically, surgery plus chemoradiation was the most costly versus surgery alone, with a relative median cost of 3.13 (P less than .001), followed by chemoradiation at 2.18 (P less than .001) surgery and radiation at 1.98 (P less than .001), and radiation alone at 1.66 (P = .013).
The treatment modalities used were driven by groups of stages, the investigators wrote. Compared with stages 0 to I, stages II to IVA were 33% more expensive, while stage IVB was 60% more expensive. Patient factors such as age, smoking, or comorbidities were not associated with cost.
Previous reported studies of cancer-specific bundled payment models have shown decreased costs and favorable outcomes, according to the researchers. Among those is an University of Texas MD Anderson Center report showing that a four-tiered model, based on treatments received and stratified by comorbidities, was feasible in a 1-year pilot study.
The current report validates those previous findings, with some differences, Dr. Ward and coauthors wrote. In particular, the three-tiered model was not stratified by Charlson comorbidity index, which did not correlate with cost in the present analysis, and it included less common disease sites than in the MD Anderson model.
“We felt it important to be inclusive of all patients seen by our multidisciplinary head and neck cancer team to keep the proposed bundled payments model as practical and simple as possible,” they wrote.
Dr. Ward reported a consulting or advisory role with AstraZeneca. Study coauthors provided disclosures related to Blue Earth Diagnostics, Merck, Varian Medical Systems, UpToDate, Gerson Lehrman Group, Osler, AlignRT, Chrysalis Biotherapeutics, and others.
SOURCE: Tom MC et al. J Oncol Pract. 2019 Apr 22. doi: 10.1200/JOP.18.00665.
While many factors can influence cost in head and neck cancer, a simple bundled payments model for the disease can be developed based solely on treatment types, researchers reported.
The number of treatment modalities was the biggest driver of cost in an analysis of 150 head and neck cancer patients. Whether those patients needed single-modality, bimodality, or trimodality treatment was in turn driven by the stage of the disease; by contrast, patient factors had no significant cost impacts, the investigators found.
Based on those findings, they developed a three-tiered cost model in which surgery or radiation was the least costly, chemoradiation or surgery plus radiation was next, and surgery plus chemoradiation was associated with the highest cost.
Basing bundled payments on treatment modality is a “simple but clinically robust model” for payment selection in head and neck cancer patients, wrote senior author Matthew C. Ward, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., and coauthors.
“A tiered system driven by treatment complexity will aid providers who seek to stratify financial risk in a simple and meaningful manner,” Dr. Ward and colleagues wrote in the Journal of Oncology Practice.
As cancer costs rise, bundled payment models seek to “incentivize value and reduce administrative waste” with a single payment per episode of care, shared by all providers contributing to that episode, they wrote. However, there have been few cancer-specific bundled payment programs described to date.
The tiered approach was based on an analysis of 150 patients with stage 0 to IVB head and neck cancer, excluding those with recurrent or metastatic disease and those treated with palliative intent. Most (58%) had stage IVA disease and the oropharynx was the tumor subsite in 48%.
Direct costs could not be published because of institutional policy, according to Dr. Ward and coauthors, who instead reported overall costs of treatment as relative median costs, or the ratio of the cost of a specific treatment versus the cost of surgery alone.
Specifically, surgery plus chemoradiation was the most costly versus surgery alone, with a relative median cost of 3.13 (P less than .001), followed by chemoradiation at 2.18 (P less than .001) surgery and radiation at 1.98 (P less than .001), and radiation alone at 1.66 (P = .013).
The treatment modalities used were driven by groups of stages, the investigators wrote. Compared with stages 0 to I, stages II to IVA were 33% more expensive, while stage IVB was 60% more expensive. Patient factors such as age, smoking, or comorbidities were not associated with cost.
Previous reported studies of cancer-specific bundled payment models have shown decreased costs and favorable outcomes, according to the researchers. Among those is an University of Texas MD Anderson Center report showing that a four-tiered model, based on treatments received and stratified by comorbidities, was feasible in a 1-year pilot study.
The current report validates those previous findings, with some differences, Dr. Ward and coauthors wrote. In particular, the three-tiered model was not stratified by Charlson comorbidity index, which did not correlate with cost in the present analysis, and it included less common disease sites than in the MD Anderson model.
“We felt it important to be inclusive of all patients seen by our multidisciplinary head and neck cancer team to keep the proposed bundled payments model as practical and simple as possible,” they wrote.
Dr. Ward reported a consulting or advisory role with AstraZeneca. Study coauthors provided disclosures related to Blue Earth Diagnostics, Merck, Varian Medical Systems, UpToDate, Gerson Lehrman Group, Osler, AlignRT, Chrysalis Biotherapeutics, and others.
SOURCE: Tom MC et al. J Oncol Pract. 2019 Apr 22. doi: 10.1200/JOP.18.00665.
While many factors can influence cost in head and neck cancer, a simple bundled payments model for the disease can be developed based solely on treatment types, researchers reported.
The number of treatment modalities was the biggest driver of cost in an analysis of 150 head and neck cancer patients. Whether those patients needed single-modality, bimodality, or trimodality treatment was in turn driven by the stage of the disease; by contrast, patient factors had no significant cost impacts, the investigators found.
Based on those findings, they developed a three-tiered cost model in which surgery or radiation was the least costly, chemoradiation or surgery plus radiation was next, and surgery plus chemoradiation was associated with the highest cost.
Basing bundled payments on treatment modality is a “simple but clinically robust model” for payment selection in head and neck cancer patients, wrote senior author Matthew C. Ward, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., and coauthors.
“A tiered system driven by treatment complexity will aid providers who seek to stratify financial risk in a simple and meaningful manner,” Dr. Ward and colleagues wrote in the Journal of Oncology Practice.
As cancer costs rise, bundled payment models seek to “incentivize value and reduce administrative waste” with a single payment per episode of care, shared by all providers contributing to that episode, they wrote. However, there have been few cancer-specific bundled payment programs described to date.
The tiered approach was based on an analysis of 150 patients with stage 0 to IVB head and neck cancer, excluding those with recurrent or metastatic disease and those treated with palliative intent. Most (58%) had stage IVA disease and the oropharynx was the tumor subsite in 48%.
Direct costs could not be published because of institutional policy, according to Dr. Ward and coauthors, who instead reported overall costs of treatment as relative median costs, or the ratio of the cost of a specific treatment versus the cost of surgery alone.
Specifically, surgery plus chemoradiation was the most costly versus surgery alone, with a relative median cost of 3.13 (P less than .001), followed by chemoradiation at 2.18 (P less than .001) surgery and radiation at 1.98 (P less than .001), and radiation alone at 1.66 (P = .013).
The treatment modalities used were driven by groups of stages, the investigators wrote. Compared with stages 0 to I, stages II to IVA were 33% more expensive, while stage IVB was 60% more expensive. Patient factors such as age, smoking, or comorbidities were not associated with cost.
Previous reported studies of cancer-specific bundled payment models have shown decreased costs and favorable outcomes, according to the researchers. Among those is an University of Texas MD Anderson Center report showing that a four-tiered model, based on treatments received and stratified by comorbidities, was feasible in a 1-year pilot study.
The current report validates those previous findings, with some differences, Dr. Ward and coauthors wrote. In particular, the three-tiered model was not stratified by Charlson comorbidity index, which did not correlate with cost in the present analysis, and it included less common disease sites than in the MD Anderson model.
“We felt it important to be inclusive of all patients seen by our multidisciplinary head and neck cancer team to keep the proposed bundled payments model as practical and simple as possible,” they wrote.
Dr. Ward reported a consulting or advisory role with AstraZeneca. Study coauthors provided disclosures related to Blue Earth Diagnostics, Merck, Varian Medical Systems, UpToDate, Gerson Lehrman Group, Osler, AlignRT, Chrysalis Biotherapeutics, and others.
SOURCE: Tom MC et al. J Oncol Pract. 2019 Apr 22. doi: 10.1200/JOP.18.00665.
FROM THE JOURNAL OF ONCOLOGY PRACTICE
Smoking found not protective against uveitis attacks in axSpA patients
Smoking does not appear to have protective effects against anterior uveitis attacks in patients with axial spondyloarthritis, according to prospective registry study data.
Both current and ex-smokers had increased uveitis rates versus never-smokers in the study, suggesting that the supposed protective effect of smoking found in previous axial spondyloarthritis studies was not causal, Sizheng Steven Zhao, MD, and his colleagues reported in the Annals of the Rheumatic Diseases.
“Spurious relationships can emerge when studies restrict to a disease population,” the researchers wrote.
The present analysis by Dr. Zhao and colleagues included 2,420 patients with axial spondyloarthritis in the British Society for Rheumatology Biologics Registry for Ankylosing Spondylitis. Of that group, 632 (26%) had a diagnosis of acute anterior uveitis over a total of 1,457 patient-years of follow-up.
Researchers looked specifically at the number of uveitis episodes per 12-month period, which ranged from 0 to 15 in the overall study cohort.
Current smokers had a 33% higher incidence of acute anterior uveitis episodes versus never-smokers, while ex-smokers had a 19% higher incidence, although the findings did not reach statistical significance, according to the researchers.
Because some studies have suggested that smoking may influence response to biologic therapy, Dr. Zhao and coinvestigators stratified patients into biologic and nonbiologic cohorts. In the biologic cohort, they found a 76% higher incidence per year of uveitis attacks for current smokers versus never-smokers, and a 29% increased incidence for ex-smokers versus never-smokers.
These findings are “consistent with increased risk of uveitis observed among smokers in the general population,” the researchers said. “Although nicotine may have anti-inflammatory properties, cigarette smoking is overall pro-inflammatory.”
Those results provide “yet another line of evidence” that should compel spondyloarthritis patients to quit smoking, the researchers added. Previous studies have suggested that smoking may increase radiographic progression and may reduce response to treatment.
The authors declared no competing interests. The registry study is supported by the British Society for Rheumatology, which has received funding from Pfizer, AbbVie, and UCB for the study.
SOURCE: Zhao SS et al. Ann Rheum Dis. 2019 Apr 20. doi: 10.1136/annrheumdis-2019-215348
Smoking does not appear to have protective effects against anterior uveitis attacks in patients with axial spondyloarthritis, according to prospective registry study data.
Both current and ex-smokers had increased uveitis rates versus never-smokers in the study, suggesting that the supposed protective effect of smoking found in previous axial spondyloarthritis studies was not causal, Sizheng Steven Zhao, MD, and his colleagues reported in the Annals of the Rheumatic Diseases.
“Spurious relationships can emerge when studies restrict to a disease population,” the researchers wrote.
The present analysis by Dr. Zhao and colleagues included 2,420 patients with axial spondyloarthritis in the British Society for Rheumatology Biologics Registry for Ankylosing Spondylitis. Of that group, 632 (26%) had a diagnosis of acute anterior uveitis over a total of 1,457 patient-years of follow-up.
Researchers looked specifically at the number of uveitis episodes per 12-month period, which ranged from 0 to 15 in the overall study cohort.
Current smokers had a 33% higher incidence of acute anterior uveitis episodes versus never-smokers, while ex-smokers had a 19% higher incidence, although the findings did not reach statistical significance, according to the researchers.
Because some studies have suggested that smoking may influence response to biologic therapy, Dr. Zhao and coinvestigators stratified patients into biologic and nonbiologic cohorts. In the biologic cohort, they found a 76% higher incidence per year of uveitis attacks for current smokers versus never-smokers, and a 29% increased incidence for ex-smokers versus never-smokers.
These findings are “consistent with increased risk of uveitis observed among smokers in the general population,” the researchers said. “Although nicotine may have anti-inflammatory properties, cigarette smoking is overall pro-inflammatory.”
Those results provide “yet another line of evidence” that should compel spondyloarthritis patients to quit smoking, the researchers added. Previous studies have suggested that smoking may increase radiographic progression and may reduce response to treatment.
The authors declared no competing interests. The registry study is supported by the British Society for Rheumatology, which has received funding from Pfizer, AbbVie, and UCB for the study.
SOURCE: Zhao SS et al. Ann Rheum Dis. 2019 Apr 20. doi: 10.1136/annrheumdis-2019-215348
Smoking does not appear to have protective effects against anterior uveitis attacks in patients with axial spondyloarthritis, according to prospective registry study data.
Both current and ex-smokers had increased uveitis rates versus never-smokers in the study, suggesting that the supposed protective effect of smoking found in previous axial spondyloarthritis studies was not causal, Sizheng Steven Zhao, MD, and his colleagues reported in the Annals of the Rheumatic Diseases.
“Spurious relationships can emerge when studies restrict to a disease population,” the researchers wrote.
The present analysis by Dr. Zhao and colleagues included 2,420 patients with axial spondyloarthritis in the British Society for Rheumatology Biologics Registry for Ankylosing Spondylitis. Of that group, 632 (26%) had a diagnosis of acute anterior uveitis over a total of 1,457 patient-years of follow-up.
Researchers looked specifically at the number of uveitis episodes per 12-month period, which ranged from 0 to 15 in the overall study cohort.
Current smokers had a 33% higher incidence of acute anterior uveitis episodes versus never-smokers, while ex-smokers had a 19% higher incidence, although the findings did not reach statistical significance, according to the researchers.
Because some studies have suggested that smoking may influence response to biologic therapy, Dr. Zhao and coinvestigators stratified patients into biologic and nonbiologic cohorts. In the biologic cohort, they found a 76% higher incidence per year of uveitis attacks for current smokers versus never-smokers, and a 29% increased incidence for ex-smokers versus never-smokers.
These findings are “consistent with increased risk of uveitis observed among smokers in the general population,” the researchers said. “Although nicotine may have anti-inflammatory properties, cigarette smoking is overall pro-inflammatory.”
Those results provide “yet another line of evidence” that should compel spondyloarthritis patients to quit smoking, the researchers added. Previous studies have suggested that smoking may increase radiographic progression and may reduce response to treatment.
The authors declared no competing interests. The registry study is supported by the British Society for Rheumatology, which has received funding from Pfizer, AbbVie, and UCB for the study.
SOURCE: Zhao SS et al. Ann Rheum Dis. 2019 Apr 20. doi: 10.1136/annrheumdis-2019-215348
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Current smokers had a 33% higher incidence of acute anterior uveitis episodes versus never-smokers, while ex-smokers had a 19% higher incidence.
Study details: Analysis including 2,420 patients with axial spondyloarthritis in the British Society for Rheumatology Biologics Registry for Ankylosing Spondylitis.
Disclosures: The authors declared no competing interests. The study is supported by the British Society for Rheumatology, which has received funding from Pfizer, AbbVie, and UCB for the study.
Source: Zhao SS et al. Ann Rheum Dis. 2019 Apr 20. doi: 10.1136/annrheumdis-2019-215348.
Medical cannabis relieved pain, decreased opioid use in elderly
results of a recent retrospective chart review suggest. Treatment with medical cannabis improved pain, sleep, anxiety, and neuropathy in patients aged 75 years of age and older, and was associated with reduced use of opioids in about one-third of cases, according to authors of the study, which will be presented at the annual meeting of the American Academy of Neurology.
“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” said lead investigator Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, N.Y., in a news release. However, additional randomized, placebo-controlled studies are needed to confirm results of this study, Dr. Mechtler added.
The chart review focused on 204 elderly patients who participated in New York State’s medical marijuana program and were followed in a neurologic outpatient setting. The cohort included 129 female and 75 male patients, ranging in age from 75 to 102 years, with a mean age of 81 years. The medical marijuana was taken by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer.
With an average exposure time of 16.8 weeks, 69% of patients experienced symptomatic benefit, according to patient self-report. The most commonly reported benefit was relief of chronic pain in 49%, while improvements in sleep, neuropathy, and anxiety were reported in 18%, 15%, and 10%, respectively. Reductions in opioid pain medication were noted in about one-third of cases, they found.
While 34% of patients had adverse effects on medical marijuana, only 21% reported adverse effects after cannabinoid doses were adjusted, investigators said. Adverse effects led to discontinuation of medical cannabis in seven patients, or 3.4% of the overall cohort. Somnolence, disequilibrium, and gastrointestinal disturbance were the most common adverse effects, occurring in 13%, 7%, and 7% of patients, respectively. Euphoria was reported in 3% of patients.
Among patients who had no reported adverse effects, the most commonly used formulation was a balanced 1:1 tincture of tetrahydrocannabinol to cannabidiol, investigators said.
Further trials could explore optimal dosing of medical cannabis in elderly patients and shed more light on adverse effects such as somnolence and disequilibrium, according to Dr. Mechtler and colleagues.
The study was supported by the Dent Family Foundation.
SOURCE: Bargnes V et al. AAN 2019, Abstract P4.1-014.
results of a recent retrospective chart review suggest. Treatment with medical cannabis improved pain, sleep, anxiety, and neuropathy in patients aged 75 years of age and older, and was associated with reduced use of opioids in about one-third of cases, according to authors of the study, which will be presented at the annual meeting of the American Academy of Neurology.
“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” said lead investigator Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, N.Y., in a news release. However, additional randomized, placebo-controlled studies are needed to confirm results of this study, Dr. Mechtler added.
The chart review focused on 204 elderly patients who participated in New York State’s medical marijuana program and were followed in a neurologic outpatient setting. The cohort included 129 female and 75 male patients, ranging in age from 75 to 102 years, with a mean age of 81 years. The medical marijuana was taken by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer.
With an average exposure time of 16.8 weeks, 69% of patients experienced symptomatic benefit, according to patient self-report. The most commonly reported benefit was relief of chronic pain in 49%, while improvements in sleep, neuropathy, and anxiety were reported in 18%, 15%, and 10%, respectively. Reductions in opioid pain medication were noted in about one-third of cases, they found.
While 34% of patients had adverse effects on medical marijuana, only 21% reported adverse effects after cannabinoid doses were adjusted, investigators said. Adverse effects led to discontinuation of medical cannabis in seven patients, or 3.4% of the overall cohort. Somnolence, disequilibrium, and gastrointestinal disturbance were the most common adverse effects, occurring in 13%, 7%, and 7% of patients, respectively. Euphoria was reported in 3% of patients.
Among patients who had no reported adverse effects, the most commonly used formulation was a balanced 1:1 tincture of tetrahydrocannabinol to cannabidiol, investigators said.
Further trials could explore optimal dosing of medical cannabis in elderly patients and shed more light on adverse effects such as somnolence and disequilibrium, according to Dr. Mechtler and colleagues.
The study was supported by the Dent Family Foundation.
SOURCE: Bargnes V et al. AAN 2019, Abstract P4.1-014.
results of a recent retrospective chart review suggest. Treatment with medical cannabis improved pain, sleep, anxiety, and neuropathy in patients aged 75 years of age and older, and was associated with reduced use of opioids in about one-third of cases, according to authors of the study, which will be presented at the annual meeting of the American Academy of Neurology.
“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” said lead investigator Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, N.Y., in a news release. However, additional randomized, placebo-controlled studies are needed to confirm results of this study, Dr. Mechtler added.
The chart review focused on 204 elderly patients who participated in New York State’s medical marijuana program and were followed in a neurologic outpatient setting. The cohort included 129 female and 75 male patients, ranging in age from 75 to 102 years, with a mean age of 81 years. The medical marijuana was taken by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer.
With an average exposure time of 16.8 weeks, 69% of patients experienced symptomatic benefit, according to patient self-report. The most commonly reported benefit was relief of chronic pain in 49%, while improvements in sleep, neuropathy, and anxiety were reported in 18%, 15%, and 10%, respectively. Reductions in opioid pain medication were noted in about one-third of cases, they found.
While 34% of patients had adverse effects on medical marijuana, only 21% reported adverse effects after cannabinoid doses were adjusted, investigators said. Adverse effects led to discontinuation of medical cannabis in seven patients, or 3.4% of the overall cohort. Somnolence, disequilibrium, and gastrointestinal disturbance were the most common adverse effects, occurring in 13%, 7%, and 7% of patients, respectively. Euphoria was reported in 3% of patients.
Among patients who had no reported adverse effects, the most commonly used formulation was a balanced 1:1 tincture of tetrahydrocannabinol to cannabidiol, investigators said.
Further trials could explore optimal dosing of medical cannabis in elderly patients and shed more light on adverse effects such as somnolence and disequilibrium, according to Dr. Mechtler and colleagues.
The study was supported by the Dent Family Foundation.
SOURCE: Bargnes V et al. AAN 2019, Abstract P4.1-014.
FROM AAN 2019
Is pro soccer a risk factor for ALS?
according to Italian researchers who reviewed trading cards of about 25,000 male professional soccer players who played in Italy. The researchers then scanned news reports to find which of those players developed the rare neurologic disease. Players who developed ALS were a much younger age at diagnosis when compared with the general population, according to the researchers, who will present their findings at the annual meeting of the American Academy of Neurology.
While the findings might implicate professional-level soccer in the development of ALS, there could be other factors at work, said lead author Ettore Beghi, MD, of the Mario Negri Institute for Pharmacological Research, Milan. “Repeated traumatic events, heavy physical exercise, and substance use could also be factors in the increased ALS risk among soccer players,” Dr. Beghi said in a news release. “In addition, genetics may play a role.”
The ALS-related deaths of several Italian pro soccer players sparked suggestions that the disease and the sport could be somehow linked, according to Dr. Beghi and colleagues. To determine whether professional soccer players are at increased ALS risk, they reviewed the archives of the country’s major soccer card publisher from the years 1959 to 2000, recording the name, date, and place of birth; field position; and team history for the tens of thousands of players they identified.
News reports revealed that 33 players in that cohort developed ALS, compared with 17.6 cases that would be expected based on Italian general population estimates, according to Dr. Beghi and colleagues.
The number of cases per 100,000 person-years was 1.9 for all the soccer players, and 4.7 for those who were younger than 45 years at diagnosis, researchers said. In general, soccer players were younger at diagnosis, with a median age of ALS onset of 43.3 years, versus 62.5 years in the general population, they added.
These findings cannot be applied to those who play soccer below the professional level, since only professional athletes were studied, Dr. Beghi said. Moreover, the results should not be construed to suggest that people avoid playing soccer, he said, adding that the researchers had few specific details on the players’ ALS diagnoses.
Patients with ALS more often report head injuries, compared with the general population, while links between exercise and ALS have been found in some studies, but not others, according to the researchers.
“Clinical and experimental observations suggest an association between ALS and use of nonsteroidal anti-inflammatory agents and dietary supplements, including branched chain amino acids,” researchers added in the abstract for their report.
The study by Dr. Beghi and colleagues was supported by the Mario Negri Institute in Milan.
Source: Beghi E et al. AAN 2019, Abstract S1.001.
according to Italian researchers who reviewed trading cards of about 25,000 male professional soccer players who played in Italy. The researchers then scanned news reports to find which of those players developed the rare neurologic disease. Players who developed ALS were a much younger age at diagnosis when compared with the general population, according to the researchers, who will present their findings at the annual meeting of the American Academy of Neurology.
While the findings might implicate professional-level soccer in the development of ALS, there could be other factors at work, said lead author Ettore Beghi, MD, of the Mario Negri Institute for Pharmacological Research, Milan. “Repeated traumatic events, heavy physical exercise, and substance use could also be factors in the increased ALS risk among soccer players,” Dr. Beghi said in a news release. “In addition, genetics may play a role.”
The ALS-related deaths of several Italian pro soccer players sparked suggestions that the disease and the sport could be somehow linked, according to Dr. Beghi and colleagues. To determine whether professional soccer players are at increased ALS risk, they reviewed the archives of the country’s major soccer card publisher from the years 1959 to 2000, recording the name, date, and place of birth; field position; and team history for the tens of thousands of players they identified.
News reports revealed that 33 players in that cohort developed ALS, compared with 17.6 cases that would be expected based on Italian general population estimates, according to Dr. Beghi and colleagues.
The number of cases per 100,000 person-years was 1.9 for all the soccer players, and 4.7 for those who were younger than 45 years at diagnosis, researchers said. In general, soccer players were younger at diagnosis, with a median age of ALS onset of 43.3 years, versus 62.5 years in the general population, they added.
These findings cannot be applied to those who play soccer below the professional level, since only professional athletes were studied, Dr. Beghi said. Moreover, the results should not be construed to suggest that people avoid playing soccer, he said, adding that the researchers had few specific details on the players’ ALS diagnoses.
Patients with ALS more often report head injuries, compared with the general population, while links between exercise and ALS have been found in some studies, but not others, according to the researchers.
“Clinical and experimental observations suggest an association between ALS and use of nonsteroidal anti-inflammatory agents and dietary supplements, including branched chain amino acids,” researchers added in the abstract for their report.
The study by Dr. Beghi and colleagues was supported by the Mario Negri Institute in Milan.
Source: Beghi E et al. AAN 2019, Abstract S1.001.
according to Italian researchers who reviewed trading cards of about 25,000 male professional soccer players who played in Italy. The researchers then scanned news reports to find which of those players developed the rare neurologic disease. Players who developed ALS were a much younger age at diagnosis when compared with the general population, according to the researchers, who will present their findings at the annual meeting of the American Academy of Neurology.
While the findings might implicate professional-level soccer in the development of ALS, there could be other factors at work, said lead author Ettore Beghi, MD, of the Mario Negri Institute for Pharmacological Research, Milan. “Repeated traumatic events, heavy physical exercise, and substance use could also be factors in the increased ALS risk among soccer players,” Dr. Beghi said in a news release. “In addition, genetics may play a role.”
The ALS-related deaths of several Italian pro soccer players sparked suggestions that the disease and the sport could be somehow linked, according to Dr. Beghi and colleagues. To determine whether professional soccer players are at increased ALS risk, they reviewed the archives of the country’s major soccer card publisher from the years 1959 to 2000, recording the name, date, and place of birth; field position; and team history for the tens of thousands of players they identified.
News reports revealed that 33 players in that cohort developed ALS, compared with 17.6 cases that would be expected based on Italian general population estimates, according to Dr. Beghi and colleagues.
The number of cases per 100,000 person-years was 1.9 for all the soccer players, and 4.7 for those who were younger than 45 years at diagnosis, researchers said. In general, soccer players were younger at diagnosis, with a median age of ALS onset of 43.3 years, versus 62.5 years in the general population, they added.
These findings cannot be applied to those who play soccer below the professional level, since only professional athletes were studied, Dr. Beghi said. Moreover, the results should not be construed to suggest that people avoid playing soccer, he said, adding that the researchers had few specific details on the players’ ALS diagnoses.
Patients with ALS more often report head injuries, compared with the general population, while links between exercise and ALS have been found in some studies, but not others, according to the researchers.
“Clinical and experimental observations suggest an association between ALS and use of nonsteroidal anti-inflammatory agents and dietary supplements, including branched chain amino acids,” researchers added in the abstract for their report.
The study by Dr. Beghi and colleagues was supported by the Mario Negri Institute in Milan.
Source: Beghi E et al. AAN 2019, Abstract S1.001.
FROM AAN 2019