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Obesity might be targetable driver of psoriatic arthritis progression
MADRID – Two sets of data presented at the European Congress of Rheumatology support the potential for weight loss to be a valuable adjunctive strategy for improving outcomes in patients with psoriatic arthritis (PsA).
One set, drawn from the ongoing PsABio observational study, correlated increasing body mass index with greater disease activity and greater disability. Another, based on patients followed for 12 months, showed that a weight loss of about 15% is associated with a significant reduction in PsA activity.
“As clinicians, we largely focus on drugs in the treatment of PsA, but these data draw attention to obesity as a potential target for improving outcomes in PsA,” said Stefan Siebert, MD, a rheumatologist at the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland).
Dr. Siebert cautioned that his data show association, not causation, but he said these data add to a growing body of evidence that provide compelling support for trials to test the premise that weight loss improves outcomes.
Although not a trial, a study by Eva Klingberg, MD, PhD, of the Sahlgrenska Academy at the University of Gothenburg (Sweden) and her associates tested this premise and showed weight loss was associated with improvement in multiple PsA activity parameters 6 and 12 months after a significant weight loss program.
“This is just one study, so we need more data, but we are already using weight loss to manage PsA in obese patients in Sweden,” said Dr. Klingberg, speaking about her work in advance of the presentation. Like Dr. Siebert, she agreed that weight loss is an important potential treatment strategy in PsA.
In the observational PsABio study, which is following patients with PsA at rheumatology centers in eight European countries, the goal of its analysis was to evaluate disease activity and outcomes in relationship to baseline weight for patients starting a biologic therapy as part of standard clinical practice. Of the 917 patients evaluated, 450 started ustekinumab (Stelara) and 467 started a tumor necrosis factor inhibitor (TNFi). The researchers had weight data for 827 of these patients.
At the time of enrollment, 40% were overweight as defined by a body mass index (BMI) ranging from 25 to 29 kg/m2, and 30.4% were obese as defined by a BMI greater than 30 kg/m2. The mean baseline BMI was 28.1 kg/m2. The mean age of the study population was 49.7 years. Slightly more than half were female.
Relative to a BMI of 30 kg/m2 or less, higher BMI at baseline is shown in multiple regression analysis to be independently and significantly linked to disease activity assessed by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA; P = .026), to patient perception of disease impact as measured by Psoriatic Arthritis Impact of Disease (PsAID-12; P less than .0001), and to greater disability as measured with Health Assessment Questionnaire Disability Index (HAQ-DI; P less than .0001).
“There are multiple sets of data that show obesity predicts who develops PsA. Our data further show that, of patients with PsA who are candidates for a biologic, those with obesity have greater disease activity,” Dr. Siebert said. “We are using all of these expensive drugs, but I think there is now a need to also focus on lifestyle interventions, in addition to drug therapy, to reduce disease activity and improve outcomes in PsA.”
The data to be presented by Dr. Klingberg provide a step in that direction. In this study, 46 PsA patients participated in a weight-loss treatment that restricted calorie intake to 640 kcal/day, and the researchers followed 39 of these patients for 1 year. The participants averaged 56 years old, and almost two-thirds were women. All enrolled patients had to have a BMI of at least 33 kg/m2, and the actual average BMI was 35 kg/m2. The median weight loss among the 39 patients followed for 1 year after the start of a 12- to 16-week weight-loss treatment was 16.1 kg, representing about 16% of their body weight at entry.
Dr. Klingberg showed that disease activity in those who achieved and maintained weight loss after the program was significant at 6 and 12 months when measured with the Psoriatic Arthritis Response Criteria (PsARC) or the American College of Rheumatology (ACR) 20, 50, and 70 criteria. In the 39 patients followed for 12 months, 36% fulfilled PsARC, and 54%, 36%, and 15% fulfilled the ACR 20, 50, and 70 responses, respectively.
“In Sweden, any obese individual can be referred for a weight loss program because of the multiple health benefits that are associated with weight reduction,” Dr. Klingberg explained. “We were able to look at patients with PsA and show that this substantially reduces the burden of their joint disease in addition to the other health advantages of losing weight.”
An improvement in symptoms is a logical expectation from reducing the mechanical strain imposed by obesity on inflamed joints, but Dr. Klingberg is more impressed by the potential for weight loss to reduce the proinflammatory signaling generated by adipose tissue. In PsA, there is evidence that weight loss reduces disease activity in the skin, as well as the joints, which supports this link.
“We need more data to document the benefits from weight loss in patients with PsA, but I think management of the comorbidities of PsA, including obesity, is something that should already be routinely discussed with patients,” Dr. Klingberg said.
Dr. Siebert has been a consultant to or speaker on behalf of AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB, and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB. Dr. Klingberg has been an advisor to Novartis, a speaker on behalf of Lilly, and has receive research funding from Roche.
Mitchel L. Zoler contributed to this report.
SOURCE: Siebert S et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69. Abstract OP0007. doi: 10.1136/annrheumdis-2019-eular.5841; Klingberg E et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69-70. Abstract OP0008. doi: 10.1136/annrheumdis-2019-eular.5551.
MADRID – Two sets of data presented at the European Congress of Rheumatology support the potential for weight loss to be a valuable adjunctive strategy for improving outcomes in patients with psoriatic arthritis (PsA).
One set, drawn from the ongoing PsABio observational study, correlated increasing body mass index with greater disease activity and greater disability. Another, based on patients followed for 12 months, showed that a weight loss of about 15% is associated with a significant reduction in PsA activity.
“As clinicians, we largely focus on drugs in the treatment of PsA, but these data draw attention to obesity as a potential target for improving outcomes in PsA,” said Stefan Siebert, MD, a rheumatologist at the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland).
Dr. Siebert cautioned that his data show association, not causation, but he said these data add to a growing body of evidence that provide compelling support for trials to test the premise that weight loss improves outcomes.
Although not a trial, a study by Eva Klingberg, MD, PhD, of the Sahlgrenska Academy at the University of Gothenburg (Sweden) and her associates tested this premise and showed weight loss was associated with improvement in multiple PsA activity parameters 6 and 12 months after a significant weight loss program.
“This is just one study, so we need more data, but we are already using weight loss to manage PsA in obese patients in Sweden,” said Dr. Klingberg, speaking about her work in advance of the presentation. Like Dr. Siebert, she agreed that weight loss is an important potential treatment strategy in PsA.
In the observational PsABio study, which is following patients with PsA at rheumatology centers in eight European countries, the goal of its analysis was to evaluate disease activity and outcomes in relationship to baseline weight for patients starting a biologic therapy as part of standard clinical practice. Of the 917 patients evaluated, 450 started ustekinumab (Stelara) and 467 started a tumor necrosis factor inhibitor (TNFi). The researchers had weight data for 827 of these patients.
At the time of enrollment, 40% were overweight as defined by a body mass index (BMI) ranging from 25 to 29 kg/m2, and 30.4% were obese as defined by a BMI greater than 30 kg/m2. The mean baseline BMI was 28.1 kg/m2. The mean age of the study population was 49.7 years. Slightly more than half were female.
Relative to a BMI of 30 kg/m2 or less, higher BMI at baseline is shown in multiple regression analysis to be independently and significantly linked to disease activity assessed by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA; P = .026), to patient perception of disease impact as measured by Psoriatic Arthritis Impact of Disease (PsAID-12; P less than .0001), and to greater disability as measured with Health Assessment Questionnaire Disability Index (HAQ-DI; P less than .0001).
“There are multiple sets of data that show obesity predicts who develops PsA. Our data further show that, of patients with PsA who are candidates for a biologic, those with obesity have greater disease activity,” Dr. Siebert said. “We are using all of these expensive drugs, but I think there is now a need to also focus on lifestyle interventions, in addition to drug therapy, to reduce disease activity and improve outcomes in PsA.”
The data to be presented by Dr. Klingberg provide a step in that direction. In this study, 46 PsA patients participated in a weight-loss treatment that restricted calorie intake to 640 kcal/day, and the researchers followed 39 of these patients for 1 year. The participants averaged 56 years old, and almost two-thirds were women. All enrolled patients had to have a BMI of at least 33 kg/m2, and the actual average BMI was 35 kg/m2. The median weight loss among the 39 patients followed for 1 year after the start of a 12- to 16-week weight-loss treatment was 16.1 kg, representing about 16% of their body weight at entry.
Dr. Klingberg showed that disease activity in those who achieved and maintained weight loss after the program was significant at 6 and 12 months when measured with the Psoriatic Arthritis Response Criteria (PsARC) or the American College of Rheumatology (ACR) 20, 50, and 70 criteria. In the 39 patients followed for 12 months, 36% fulfilled PsARC, and 54%, 36%, and 15% fulfilled the ACR 20, 50, and 70 responses, respectively.
“In Sweden, any obese individual can be referred for a weight loss program because of the multiple health benefits that are associated with weight reduction,” Dr. Klingberg explained. “We were able to look at patients with PsA and show that this substantially reduces the burden of their joint disease in addition to the other health advantages of losing weight.”
An improvement in symptoms is a logical expectation from reducing the mechanical strain imposed by obesity on inflamed joints, but Dr. Klingberg is more impressed by the potential for weight loss to reduce the proinflammatory signaling generated by adipose tissue. In PsA, there is evidence that weight loss reduces disease activity in the skin, as well as the joints, which supports this link.
“We need more data to document the benefits from weight loss in patients with PsA, but I think management of the comorbidities of PsA, including obesity, is something that should already be routinely discussed with patients,” Dr. Klingberg said.
Dr. Siebert has been a consultant to or speaker on behalf of AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB, and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB. Dr. Klingberg has been an advisor to Novartis, a speaker on behalf of Lilly, and has receive research funding from Roche.
Mitchel L. Zoler contributed to this report.
SOURCE: Siebert S et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69. Abstract OP0007. doi: 10.1136/annrheumdis-2019-eular.5841; Klingberg E et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69-70. Abstract OP0008. doi: 10.1136/annrheumdis-2019-eular.5551.
MADRID – Two sets of data presented at the European Congress of Rheumatology support the potential for weight loss to be a valuable adjunctive strategy for improving outcomes in patients with psoriatic arthritis (PsA).
One set, drawn from the ongoing PsABio observational study, correlated increasing body mass index with greater disease activity and greater disability. Another, based on patients followed for 12 months, showed that a weight loss of about 15% is associated with a significant reduction in PsA activity.
“As clinicians, we largely focus on drugs in the treatment of PsA, but these data draw attention to obesity as a potential target for improving outcomes in PsA,” said Stefan Siebert, MD, a rheumatologist at the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland).
Dr. Siebert cautioned that his data show association, not causation, but he said these data add to a growing body of evidence that provide compelling support for trials to test the premise that weight loss improves outcomes.
Although not a trial, a study by Eva Klingberg, MD, PhD, of the Sahlgrenska Academy at the University of Gothenburg (Sweden) and her associates tested this premise and showed weight loss was associated with improvement in multiple PsA activity parameters 6 and 12 months after a significant weight loss program.
“This is just one study, so we need more data, but we are already using weight loss to manage PsA in obese patients in Sweden,” said Dr. Klingberg, speaking about her work in advance of the presentation. Like Dr. Siebert, she agreed that weight loss is an important potential treatment strategy in PsA.
In the observational PsABio study, which is following patients with PsA at rheumatology centers in eight European countries, the goal of its analysis was to evaluate disease activity and outcomes in relationship to baseline weight for patients starting a biologic therapy as part of standard clinical practice. Of the 917 patients evaluated, 450 started ustekinumab (Stelara) and 467 started a tumor necrosis factor inhibitor (TNFi). The researchers had weight data for 827 of these patients.
At the time of enrollment, 40% were overweight as defined by a body mass index (BMI) ranging from 25 to 29 kg/m2, and 30.4% were obese as defined by a BMI greater than 30 kg/m2. The mean baseline BMI was 28.1 kg/m2. The mean age of the study population was 49.7 years. Slightly more than half were female.
Relative to a BMI of 30 kg/m2 or less, higher BMI at baseline is shown in multiple regression analysis to be independently and significantly linked to disease activity assessed by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA; P = .026), to patient perception of disease impact as measured by Psoriatic Arthritis Impact of Disease (PsAID-12; P less than .0001), and to greater disability as measured with Health Assessment Questionnaire Disability Index (HAQ-DI; P less than .0001).
“There are multiple sets of data that show obesity predicts who develops PsA. Our data further show that, of patients with PsA who are candidates for a biologic, those with obesity have greater disease activity,” Dr. Siebert said. “We are using all of these expensive drugs, but I think there is now a need to also focus on lifestyle interventions, in addition to drug therapy, to reduce disease activity and improve outcomes in PsA.”
The data to be presented by Dr. Klingberg provide a step in that direction. In this study, 46 PsA patients participated in a weight-loss treatment that restricted calorie intake to 640 kcal/day, and the researchers followed 39 of these patients for 1 year. The participants averaged 56 years old, and almost two-thirds were women. All enrolled patients had to have a BMI of at least 33 kg/m2, and the actual average BMI was 35 kg/m2. The median weight loss among the 39 patients followed for 1 year after the start of a 12- to 16-week weight-loss treatment was 16.1 kg, representing about 16% of their body weight at entry.
Dr. Klingberg showed that disease activity in those who achieved and maintained weight loss after the program was significant at 6 and 12 months when measured with the Psoriatic Arthritis Response Criteria (PsARC) or the American College of Rheumatology (ACR) 20, 50, and 70 criteria. In the 39 patients followed for 12 months, 36% fulfilled PsARC, and 54%, 36%, and 15% fulfilled the ACR 20, 50, and 70 responses, respectively.
“In Sweden, any obese individual can be referred for a weight loss program because of the multiple health benefits that are associated with weight reduction,” Dr. Klingberg explained. “We were able to look at patients with PsA and show that this substantially reduces the burden of their joint disease in addition to the other health advantages of losing weight.”
An improvement in symptoms is a logical expectation from reducing the mechanical strain imposed by obesity on inflamed joints, but Dr. Klingberg is more impressed by the potential for weight loss to reduce the proinflammatory signaling generated by adipose tissue. In PsA, there is evidence that weight loss reduces disease activity in the skin, as well as the joints, which supports this link.
“We need more data to document the benefits from weight loss in patients with PsA, but I think management of the comorbidities of PsA, including obesity, is something that should already be routinely discussed with patients,” Dr. Klingberg said.
Dr. Siebert has been a consultant to or speaker on behalf of AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB, and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB. Dr. Klingberg has been an advisor to Novartis, a speaker on behalf of Lilly, and has receive research funding from Roche.
Mitchel L. Zoler contributed to this report.
SOURCE: Siebert S et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69. Abstract OP0007. doi: 10.1136/annrheumdis-2019-eular.5841; Klingberg E et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69-70. Abstract OP0008. doi: 10.1136/annrheumdis-2019-eular.5551.
REPORTING FROM EULAR 2019 CONGRESS
Substantial reductions in HPV infections, CIN2+ after vaccination
The introduction of the human papillomavirus according to a meta-analysis of data from more than 60 million individuals worldwide.
Mélanie Drolet, PhD, from the Centre de recherche du CHU de Québec–Université Laval, and coauthors of the HPV Vaccination Impact Study Group reported the results of a systematic review and meta-analysis of 65 studies showing pre- and postvaccination frequency of at least one HPV-related endpoint published in the Lancet. The studies were conducted in 14 high-income countries, 12 of which were vaccinating only women and girls, with the results at 5-8 years published in the Lancet.
At 5-8 years after a vaccination program was implemented, there was a significant 83% reduction in the prevalence of HPV 16 and 18, both of which are targeted by the vaccine, among girls aged 13-19 years; a 66% reduction among women aged 20-24 years; and a 37% reduction in women aged 25-29 years, even though most of these women were unvaccinated.
There also were significant decreases at 5-8 years in the prevalence of HPV subtypes 31, 33, and 45, which are not included in the vaccine but against which the vaccine appears to offer cross-protection. Among girls aged 13-19 years, there was a significant 54% reduction in the prevalence of these subtypes, among women aged 20-24 years there was a nonsignificant 28% decrease, but among women aged 25-29 years, there was no significant decrease.
The analysis also found significant declines in the prevalence of cervical intraepithelial neoplasias (CINs) of grade 2 or above. At 5-9 years after vaccination was introduced, CIN2+ decreased by 51% among girls aged 15-19 years who also were screened for cervical cancer, and by 31% among women aged 20-24 years.
However, over the same time period, the rates of CIN2+ increased by a significant 19% among mostly unvaccinated women aged 25-29 years and 23% among mostly unvaccinated women aged 30-39 years, despite both groups being screened for cervical abnormalities.
While most of the countries in the study vaccinated only girls and women, two studies did find nonsignificant decreases in the prevalence of HPV 16, 18, 31, 33, and 45 among boys aged 16-19 years, but not among men aged 20-24 years.
HPV vaccination also was associated with significant declines in the incidence of anogenital warts among both males and females. In the first 4 years alone, vaccination was associated with significant reductions in anogenital wart diagnoses among females aged 15-29 years, as well as nonsignificant but “substantial” reductions in unvaccinated boys aged 15-19 years.
After 5-8 years, anogenital wart diagnoses decreased by 67% among girls aged 15-19 years, significantly by 54% among women aged 20-24 years, and 31% among women aged 25-29 years – all significant changes. Among boys aged 15-19 years, anogenital wart diagnoses decreased by a significant 48%, and among men aged 20-24 years they decreased by a significant 32%.
The decreases in anogenital wart diagnoses were even greater in countries that implemented vaccination among multiple cohorts simultaneously and achieved high vaccination coverage, compared with countries that vaccinated only one cohort at a time or had low routine vaccination coverage.
“Our study is the first to show the real-world additional benefit of multicohort HPV vaccination and high routine vaccination coverage, and the fast and substantial herd effects of vaccination in countries which implement these measures,” wrote Dr. Drolet and coauthors. “The greater impact of multicohort vaccination was similar when restricting the analyses to countries with high routine vaccination coverage.”
They pointed to the World Health Organization’s recently revised position on HPV vaccination, which now recommends vaccination of multiple cohorts of girls aged 9-14 years, although they raised the question of what might be the optimal number of age cohorts. “Number needed to vaccinate and cost-effectiveness analyses in high-income countries suggest that vaccinating multiple cohorts of individuals up to 18 years of age is highly efficient and cost effective.”
This analysis by Drolet et al. “provides compelling evidence for HPV vaccine efficacy on all outcomes explored and for almost all age strata,” Dr. Silvia de Sanjose, of PATH in Seattle, and Dr. Sinead Delany-Moretlwe of the Wits Reproductive Health and HIV Institute at the University of Witwatersrand in Johannesburg, said in an accompanying editorial (Lancet. 2019 Jun 26. doi: 10.1016/ S0140-6736[19]30549-5). This study shows just how effective HPV vaccination can be across a range of outcomes and ages, and also demonstrates the herd immunity benefits, particularly when multiple cohorts are vaccinated and there is high vaccination coverage.
One key limitation of this analysis is the lack of data from low- and middle-income countries. The data by Drolet et al. “emphasise the importance of redoubling our efforts to tackle the fiscal, supply, and programmatic barriers that currently limit HPV vaccine programmes; with these efforts, HPV vaccination could become a hallmark investment of cancer prevention in the 21st century,” Dr. de Sanjose and Dr. Delany-Moretlwe concluded.
The study was funded by WHO, Canadian Institutes of Health Research, and Fonds de recherche du Québec–Santé. No conflicts of interest were declared.
Dr. de Sanjose declared previous institutional support from Merck.
SOURCE: Drolet M et al. Lancet 2019 Jun 26. doi: 10.1016/ S0140-6736(19)30298-3.
The introduction of the human papillomavirus according to a meta-analysis of data from more than 60 million individuals worldwide.
Mélanie Drolet, PhD, from the Centre de recherche du CHU de Québec–Université Laval, and coauthors of the HPV Vaccination Impact Study Group reported the results of a systematic review and meta-analysis of 65 studies showing pre- and postvaccination frequency of at least one HPV-related endpoint published in the Lancet. The studies were conducted in 14 high-income countries, 12 of which were vaccinating only women and girls, with the results at 5-8 years published in the Lancet.
At 5-8 years after a vaccination program was implemented, there was a significant 83% reduction in the prevalence of HPV 16 and 18, both of which are targeted by the vaccine, among girls aged 13-19 years; a 66% reduction among women aged 20-24 years; and a 37% reduction in women aged 25-29 years, even though most of these women were unvaccinated.
There also were significant decreases at 5-8 years in the prevalence of HPV subtypes 31, 33, and 45, which are not included in the vaccine but against which the vaccine appears to offer cross-protection. Among girls aged 13-19 years, there was a significant 54% reduction in the prevalence of these subtypes, among women aged 20-24 years there was a nonsignificant 28% decrease, but among women aged 25-29 years, there was no significant decrease.
The analysis also found significant declines in the prevalence of cervical intraepithelial neoplasias (CINs) of grade 2 or above. At 5-9 years after vaccination was introduced, CIN2+ decreased by 51% among girls aged 15-19 years who also were screened for cervical cancer, and by 31% among women aged 20-24 years.
However, over the same time period, the rates of CIN2+ increased by a significant 19% among mostly unvaccinated women aged 25-29 years and 23% among mostly unvaccinated women aged 30-39 years, despite both groups being screened for cervical abnormalities.
While most of the countries in the study vaccinated only girls and women, two studies did find nonsignificant decreases in the prevalence of HPV 16, 18, 31, 33, and 45 among boys aged 16-19 years, but not among men aged 20-24 years.
HPV vaccination also was associated with significant declines in the incidence of anogenital warts among both males and females. In the first 4 years alone, vaccination was associated with significant reductions in anogenital wart diagnoses among females aged 15-29 years, as well as nonsignificant but “substantial” reductions in unvaccinated boys aged 15-19 years.
After 5-8 years, anogenital wart diagnoses decreased by 67% among girls aged 15-19 years, significantly by 54% among women aged 20-24 years, and 31% among women aged 25-29 years – all significant changes. Among boys aged 15-19 years, anogenital wart diagnoses decreased by a significant 48%, and among men aged 20-24 years they decreased by a significant 32%.
The decreases in anogenital wart diagnoses were even greater in countries that implemented vaccination among multiple cohorts simultaneously and achieved high vaccination coverage, compared with countries that vaccinated only one cohort at a time or had low routine vaccination coverage.
“Our study is the first to show the real-world additional benefit of multicohort HPV vaccination and high routine vaccination coverage, and the fast and substantial herd effects of vaccination in countries which implement these measures,” wrote Dr. Drolet and coauthors. “The greater impact of multicohort vaccination was similar when restricting the analyses to countries with high routine vaccination coverage.”
They pointed to the World Health Organization’s recently revised position on HPV vaccination, which now recommends vaccination of multiple cohorts of girls aged 9-14 years, although they raised the question of what might be the optimal number of age cohorts. “Number needed to vaccinate and cost-effectiveness analyses in high-income countries suggest that vaccinating multiple cohorts of individuals up to 18 years of age is highly efficient and cost effective.”
This analysis by Drolet et al. “provides compelling evidence for HPV vaccine efficacy on all outcomes explored and for almost all age strata,” Dr. Silvia de Sanjose, of PATH in Seattle, and Dr. Sinead Delany-Moretlwe of the Wits Reproductive Health and HIV Institute at the University of Witwatersrand in Johannesburg, said in an accompanying editorial (Lancet. 2019 Jun 26. doi: 10.1016/ S0140-6736[19]30549-5). This study shows just how effective HPV vaccination can be across a range of outcomes and ages, and also demonstrates the herd immunity benefits, particularly when multiple cohorts are vaccinated and there is high vaccination coverage.
One key limitation of this analysis is the lack of data from low- and middle-income countries. The data by Drolet et al. “emphasise the importance of redoubling our efforts to tackle the fiscal, supply, and programmatic barriers that currently limit HPV vaccine programmes; with these efforts, HPV vaccination could become a hallmark investment of cancer prevention in the 21st century,” Dr. de Sanjose and Dr. Delany-Moretlwe concluded.
The study was funded by WHO, Canadian Institutes of Health Research, and Fonds de recherche du Québec–Santé. No conflicts of interest were declared.
Dr. de Sanjose declared previous institutional support from Merck.
SOURCE: Drolet M et al. Lancet 2019 Jun 26. doi: 10.1016/ S0140-6736(19)30298-3.
The introduction of the human papillomavirus according to a meta-analysis of data from more than 60 million individuals worldwide.
Mélanie Drolet, PhD, from the Centre de recherche du CHU de Québec–Université Laval, and coauthors of the HPV Vaccination Impact Study Group reported the results of a systematic review and meta-analysis of 65 studies showing pre- and postvaccination frequency of at least one HPV-related endpoint published in the Lancet. The studies were conducted in 14 high-income countries, 12 of which were vaccinating only women and girls, with the results at 5-8 years published in the Lancet.
At 5-8 years after a vaccination program was implemented, there was a significant 83% reduction in the prevalence of HPV 16 and 18, both of which are targeted by the vaccine, among girls aged 13-19 years; a 66% reduction among women aged 20-24 years; and a 37% reduction in women aged 25-29 years, even though most of these women were unvaccinated.
There also were significant decreases at 5-8 years in the prevalence of HPV subtypes 31, 33, and 45, which are not included in the vaccine but against which the vaccine appears to offer cross-protection. Among girls aged 13-19 years, there was a significant 54% reduction in the prevalence of these subtypes, among women aged 20-24 years there was a nonsignificant 28% decrease, but among women aged 25-29 years, there was no significant decrease.
The analysis also found significant declines in the prevalence of cervical intraepithelial neoplasias (CINs) of grade 2 or above. At 5-9 years after vaccination was introduced, CIN2+ decreased by 51% among girls aged 15-19 years who also were screened for cervical cancer, and by 31% among women aged 20-24 years.
However, over the same time period, the rates of CIN2+ increased by a significant 19% among mostly unvaccinated women aged 25-29 years and 23% among mostly unvaccinated women aged 30-39 years, despite both groups being screened for cervical abnormalities.
While most of the countries in the study vaccinated only girls and women, two studies did find nonsignificant decreases in the prevalence of HPV 16, 18, 31, 33, and 45 among boys aged 16-19 years, but not among men aged 20-24 years.
HPV vaccination also was associated with significant declines in the incidence of anogenital warts among both males and females. In the first 4 years alone, vaccination was associated with significant reductions in anogenital wart diagnoses among females aged 15-29 years, as well as nonsignificant but “substantial” reductions in unvaccinated boys aged 15-19 years.
After 5-8 years, anogenital wart diagnoses decreased by 67% among girls aged 15-19 years, significantly by 54% among women aged 20-24 years, and 31% among women aged 25-29 years – all significant changes. Among boys aged 15-19 years, anogenital wart diagnoses decreased by a significant 48%, and among men aged 20-24 years they decreased by a significant 32%.
The decreases in anogenital wart diagnoses were even greater in countries that implemented vaccination among multiple cohorts simultaneously and achieved high vaccination coverage, compared with countries that vaccinated only one cohort at a time or had low routine vaccination coverage.
“Our study is the first to show the real-world additional benefit of multicohort HPV vaccination and high routine vaccination coverage, and the fast and substantial herd effects of vaccination in countries which implement these measures,” wrote Dr. Drolet and coauthors. “The greater impact of multicohort vaccination was similar when restricting the analyses to countries with high routine vaccination coverage.”
They pointed to the World Health Organization’s recently revised position on HPV vaccination, which now recommends vaccination of multiple cohorts of girls aged 9-14 years, although they raised the question of what might be the optimal number of age cohorts. “Number needed to vaccinate and cost-effectiveness analyses in high-income countries suggest that vaccinating multiple cohorts of individuals up to 18 years of age is highly efficient and cost effective.”
This analysis by Drolet et al. “provides compelling evidence for HPV vaccine efficacy on all outcomes explored and for almost all age strata,” Dr. Silvia de Sanjose, of PATH in Seattle, and Dr. Sinead Delany-Moretlwe of the Wits Reproductive Health and HIV Institute at the University of Witwatersrand in Johannesburg, said in an accompanying editorial (Lancet. 2019 Jun 26. doi: 10.1016/ S0140-6736[19]30549-5). This study shows just how effective HPV vaccination can be across a range of outcomes and ages, and also demonstrates the herd immunity benefits, particularly when multiple cohorts are vaccinated and there is high vaccination coverage.
One key limitation of this analysis is the lack of data from low- and middle-income countries. The data by Drolet et al. “emphasise the importance of redoubling our efforts to tackle the fiscal, supply, and programmatic barriers that currently limit HPV vaccine programmes; with these efforts, HPV vaccination could become a hallmark investment of cancer prevention in the 21st century,” Dr. de Sanjose and Dr. Delany-Moretlwe concluded.
The study was funded by WHO, Canadian Institutes of Health Research, and Fonds de recherche du Québec–Santé. No conflicts of interest were declared.
Dr. de Sanjose declared previous institutional support from Merck.
SOURCE: Drolet M et al. Lancet 2019 Jun 26. doi: 10.1016/ S0140-6736(19)30298-3.
FROM THE LANCET
Key clinical point: Significant declines in HPV infections, CIN2+, and anogenital warts have occurred after the introduction of HPV vaccine programs, some because of herd effects.
Major finding: The HPV vaccination program is associated with a significant 83% reduction in the prevalence of HPV 16 and 18 among girls aged 13-19 years in 14 high-income countries.
Study details: Systematic review and meta-analysis of 65 studies involving more than 60 million individuals in 14 countries.
Disclosures: The study was funded by World Health Organization, Canadian Institutes of Health Research, and Fonds de recherche du Québec – Santé. No conflicts of interest were declared.
Source: Drolet M et al. Lancet 2019 Jun 26. doi: 10.1016/ S0140-6736(19)30298-3.
Surprise billing legislation passes Senate committee
A bill aimed at ending the practice of surprise billing, along with a number of other health care cost-containment measures, passed by an overwhelming majority during a mark-up session of the Senate Health, Education, Labor, and Pensions Committee.
S. 1895, the Lower Health Care Costs Act of 2019, passed 20-3; Sens. Rand Paul (R-Ky.), Bernie Sanders (D-Ver.) and Elizabeth Warren (D-Mass.) voted against it.
A summary of the bill’s provisions can be found here.
With Sen. Sanders and Sen. Warren not present, presumably out to prepare for the Democratic presidential nominee debates and voting by proxy, only Sen. Paul was present to speak against the bill. He questioned whether it would have any impact on lowering health care cost.
Among other provisions, the bill would ban all gag clauses that would keep pricing data from being released; all anticompetitive clauses in facility and insurance contracts that would otherwise limit access to higher-quality, lower-cost care; would designate a nongovernment entity focused on price transparency; and would improve the accuracy of directory information.
But government-induced transparency is not the solution, Sen. Paul said.
He called it a “fallacy” that “you can mandate transparency, and you’ll create a marketplace.” Rather, you need to create a marketplace, and transparency will naturally follow, he said.
Sen. Paul noted that just having institutions publishing prices that no one pays and prices that are not freely fluctuating “doesn’t work.”
“The irony here is that, when you have no insurance involved, you actually have a marketplace,” he said. “The people without insurance are the only true marketplace,” he said, adding that those with high deductibles would also fall into that category.
The crux of S. 1895 is protections to end so-called “surprise bills” that occur when patients receive medical services from out-of-network health care professionals at in-network hospitals. These out-of-network services are not constrained by prior agreements and can add up to tens of thousands of dollars.
“There are those who have seen the history of price controls and know that you never get what you intended,” he said, and predicted that this could lead to a shortage of physicians.
The American Medical Association also criticized the surprise billing provisions of the bill.
In a June 25 letter, the AMA noted that “the approach outlined in S. 1895 fails to address some of the fundamental reasons why surprise billing occurs – inadequate provider networks, higher patient-cost sharing requirements for out-of-network services, and noncompetitive local markets that empower plans to offer take-it-or-leave-it contracts.”
AMA also criticized the use of benchmark pricing to settle out-of-network billing issues. “By setting a payment maximum at the individual plans’ median in-network amount, insurers will have even less incentive to negotiate contracts with individual providers,” according to the letter. “They can drive down the median in-network amount by simply dropping from their networks providers who are currently paid above the median. Or, they can simply stop negotiating altogether, knowing that their financial obligation is limited to their own median in-network payment amounts.”
The Physicians Advocacy Institute agreed. In a June 26 statement, the organization stated that it remains “deeply concerned that arbitrary, government-set payment benchmarks championed by the health insurance industry will further undermine provider networks and devastate patients’ access to critical medical services.”
A collective of hospital organizations, including the Federation of American Hospitals and the American Hospital Association also opposed the use of benchmark pricing.
In a June 25 letter to committee leadership, the groups stated that they are “concerned that the rate-setting provision of the legislation is a plan-determined, nontransparent process that will upend private payment negotiation. A default rate will become the payment ceiling and remove incentives for insurers to develop comprehensive networks, as there are already increasing numbers of narrow network products offered that exclude certain types of providers.”
The bill also addresses the cost of prescription drugs, including providing clearer information about patents, ensuring a more timely access to generics, altering exclusivity rules to help get generics to market quicker, reporting requirements for price increases, and a number of other provisions aimed at increasing competition in an effort to lower drug pricing.
Other areas covered by the bill include more oversight of pharmacy benefit managers, strengthening parity in mental health laws, and a number of provisions aimed at public health and health information technology.
A bill aimed at ending the practice of surprise billing, along with a number of other health care cost-containment measures, passed by an overwhelming majority during a mark-up session of the Senate Health, Education, Labor, and Pensions Committee.
S. 1895, the Lower Health Care Costs Act of 2019, passed 20-3; Sens. Rand Paul (R-Ky.), Bernie Sanders (D-Ver.) and Elizabeth Warren (D-Mass.) voted against it.
A summary of the bill’s provisions can be found here.
With Sen. Sanders and Sen. Warren not present, presumably out to prepare for the Democratic presidential nominee debates and voting by proxy, only Sen. Paul was present to speak against the bill. He questioned whether it would have any impact on lowering health care cost.
Among other provisions, the bill would ban all gag clauses that would keep pricing data from being released; all anticompetitive clauses in facility and insurance contracts that would otherwise limit access to higher-quality, lower-cost care; would designate a nongovernment entity focused on price transparency; and would improve the accuracy of directory information.
But government-induced transparency is not the solution, Sen. Paul said.
He called it a “fallacy” that “you can mandate transparency, and you’ll create a marketplace.” Rather, you need to create a marketplace, and transparency will naturally follow, he said.
Sen. Paul noted that just having institutions publishing prices that no one pays and prices that are not freely fluctuating “doesn’t work.”
“The irony here is that, when you have no insurance involved, you actually have a marketplace,” he said. “The people without insurance are the only true marketplace,” he said, adding that those with high deductibles would also fall into that category.
The crux of S. 1895 is protections to end so-called “surprise bills” that occur when patients receive medical services from out-of-network health care professionals at in-network hospitals. These out-of-network services are not constrained by prior agreements and can add up to tens of thousands of dollars.
“There are those who have seen the history of price controls and know that you never get what you intended,” he said, and predicted that this could lead to a shortage of physicians.
The American Medical Association also criticized the surprise billing provisions of the bill.
In a June 25 letter, the AMA noted that “the approach outlined in S. 1895 fails to address some of the fundamental reasons why surprise billing occurs – inadequate provider networks, higher patient-cost sharing requirements for out-of-network services, and noncompetitive local markets that empower plans to offer take-it-or-leave-it contracts.”
AMA also criticized the use of benchmark pricing to settle out-of-network billing issues. “By setting a payment maximum at the individual plans’ median in-network amount, insurers will have even less incentive to negotiate contracts with individual providers,” according to the letter. “They can drive down the median in-network amount by simply dropping from their networks providers who are currently paid above the median. Or, they can simply stop negotiating altogether, knowing that their financial obligation is limited to their own median in-network payment amounts.”
The Physicians Advocacy Institute agreed. In a June 26 statement, the organization stated that it remains “deeply concerned that arbitrary, government-set payment benchmarks championed by the health insurance industry will further undermine provider networks and devastate patients’ access to critical medical services.”
A collective of hospital organizations, including the Federation of American Hospitals and the American Hospital Association also opposed the use of benchmark pricing.
In a June 25 letter to committee leadership, the groups stated that they are “concerned that the rate-setting provision of the legislation is a plan-determined, nontransparent process that will upend private payment negotiation. A default rate will become the payment ceiling and remove incentives for insurers to develop comprehensive networks, as there are already increasing numbers of narrow network products offered that exclude certain types of providers.”
The bill also addresses the cost of prescription drugs, including providing clearer information about patents, ensuring a more timely access to generics, altering exclusivity rules to help get generics to market quicker, reporting requirements for price increases, and a number of other provisions aimed at increasing competition in an effort to lower drug pricing.
Other areas covered by the bill include more oversight of pharmacy benefit managers, strengthening parity in mental health laws, and a number of provisions aimed at public health and health information technology.
A bill aimed at ending the practice of surprise billing, along with a number of other health care cost-containment measures, passed by an overwhelming majority during a mark-up session of the Senate Health, Education, Labor, and Pensions Committee.
S. 1895, the Lower Health Care Costs Act of 2019, passed 20-3; Sens. Rand Paul (R-Ky.), Bernie Sanders (D-Ver.) and Elizabeth Warren (D-Mass.) voted against it.
A summary of the bill’s provisions can be found here.
With Sen. Sanders and Sen. Warren not present, presumably out to prepare for the Democratic presidential nominee debates and voting by proxy, only Sen. Paul was present to speak against the bill. He questioned whether it would have any impact on lowering health care cost.
Among other provisions, the bill would ban all gag clauses that would keep pricing data from being released; all anticompetitive clauses in facility and insurance contracts that would otherwise limit access to higher-quality, lower-cost care; would designate a nongovernment entity focused on price transparency; and would improve the accuracy of directory information.
But government-induced transparency is not the solution, Sen. Paul said.
He called it a “fallacy” that “you can mandate transparency, and you’ll create a marketplace.” Rather, you need to create a marketplace, and transparency will naturally follow, he said.
Sen. Paul noted that just having institutions publishing prices that no one pays and prices that are not freely fluctuating “doesn’t work.”
“The irony here is that, when you have no insurance involved, you actually have a marketplace,” he said. “The people without insurance are the only true marketplace,” he said, adding that those with high deductibles would also fall into that category.
The crux of S. 1895 is protections to end so-called “surprise bills” that occur when patients receive medical services from out-of-network health care professionals at in-network hospitals. These out-of-network services are not constrained by prior agreements and can add up to tens of thousands of dollars.
“There are those who have seen the history of price controls and know that you never get what you intended,” he said, and predicted that this could lead to a shortage of physicians.
The American Medical Association also criticized the surprise billing provisions of the bill.
In a June 25 letter, the AMA noted that “the approach outlined in S. 1895 fails to address some of the fundamental reasons why surprise billing occurs – inadequate provider networks, higher patient-cost sharing requirements for out-of-network services, and noncompetitive local markets that empower plans to offer take-it-or-leave-it contracts.”
AMA also criticized the use of benchmark pricing to settle out-of-network billing issues. “By setting a payment maximum at the individual plans’ median in-network amount, insurers will have even less incentive to negotiate contracts with individual providers,” according to the letter. “They can drive down the median in-network amount by simply dropping from their networks providers who are currently paid above the median. Or, they can simply stop negotiating altogether, knowing that their financial obligation is limited to their own median in-network payment amounts.”
The Physicians Advocacy Institute agreed. In a June 26 statement, the organization stated that it remains “deeply concerned that arbitrary, government-set payment benchmarks championed by the health insurance industry will further undermine provider networks and devastate patients’ access to critical medical services.”
A collective of hospital organizations, including the Federation of American Hospitals and the American Hospital Association also opposed the use of benchmark pricing.
In a June 25 letter to committee leadership, the groups stated that they are “concerned that the rate-setting provision of the legislation is a plan-determined, nontransparent process that will upend private payment negotiation. A default rate will become the payment ceiling and remove incentives for insurers to develop comprehensive networks, as there are already increasing numbers of narrow network products offered that exclude certain types of providers.”
The bill also addresses the cost of prescription drugs, including providing clearer information about patents, ensuring a more timely access to generics, altering exclusivity rules to help get generics to market quicker, reporting requirements for price increases, and a number of other provisions aimed at increasing competition in an effort to lower drug pricing.
Other areas covered by the bill include more oversight of pharmacy benefit managers, strengthening parity in mental health laws, and a number of provisions aimed at public health and health information technology.
REPORTING FROM A SENATE COMMITTEE MEETING
The 21st Century Cures Act: Tearing down fortresses to put patients first
"A fortress not only protects those inside of it, but it also enslaves them to work.”
– Anthony T. Hincks
As physicians, we spend a great deal of time intending to do our best for the people we serve. We believe fundamentally in the idea that our patients come first, and we toil daily to exercise that belief. We also want our patients to feel they are driving their care as active participants along the journey. Yet time and time again, despite our greatest attempts, those efforts are stymied by the state of modern medicine;
Over the past 10 years, we have done a tremendous job of constructing expensive fortresses around patient information known as electronic health records (EHRs). Billions of dollars have been spent implementing, upgrading, and optimizing. In spite of this, physicians are increasingly frustrated by EHRs (and in many cases, long to return to the days of paper). It isn’t surprising, then, that patients are frustrated as well. We use terms such as “patient-centered care,” but patients feel like they are not in the center at all. Instead, they can find themselves feeling like complete outsiders, at the mercy of the medical juggernaut to make sure they have the appropriate information when they need it. There are several issues that contribute to the frustrations of physicians and patients, but two in particular warrant attention. The first is the diversity of Health IT systems and ongoing issues with EHR interoperability. The second is a provincial attitude surrounding transparency and medical record ownership. We will discuss both of these here, as well as recent legislation designed to advance both concerns.
We have written in previous columns about the many challenges of interoperability. Electronic health records, sold by different vendors, typically won’t “talk” to each other. In spite of years of maturation, issues of compatibility remain. Patient data locked inside of one EHR is not easily accessible by a physician using a different EHR. While efforts have been made to streamline information sharing, there are still many fortresses that cannot be breached.
Bridging the moat
The 21st Century Cures Act, enacted by Congress in December of 2016, seeks to define and require interoperability while addressing many other significant problems in health care. According to the legislation, true interoperability means that health IT should enable the secure exchange of electronic health information with other electronic record systems without special effort on the part of the user; the process should be seamless and shouldn’t be cumbersome for physicians or patients. It also must be fully supported by EHR vendors, but those vendors have been expressing significant concerns with the ways in which the act is being interpreted.
In a recent blog post, the HIMSS Electronic Health Record Association – a consortium of vendors including Epic, Allscripts, eClinicalWorks, as well as several others – expressed “significant concerns regarding timelines, ambiguous language, disincentives for innovation, and definitions related to information blocking.”1 This is not surprising, as the onus for improving interoperability falls squarely on their shoulders, and the work to get there is arduous. Regardless of one’s interpretation, the goal of the Cures act is clear: Arrive at true interoperability in the shortest period of time, while eliminating barriers that prevent patients from accessing their health records. In other words, it asks for the avoidance of “information blocking.”
Breaching the gate
Information blocking, as defined by the Cures Act, is “a practice by a health care provider, health IT developer, health information exchange, or health information network that … is likely to interfere with, prevent, or materially discourage access, exchange, or use of electronic health information.”2 This practice is explicitly prohibited by the legislation – and is ethically wrong – yet it continues to occur implicitly every day as it has for many years. Even if unintentional and solely because of the growing complexity of our information systems, it makes accessing health information incredibly cumbersome for patients. Even worse, attempts to improve patients’ ability to access their health records have only created additional obstacles.
HIPAA (the Health Insurance Portability and Accountability Act of 1996) was designed to protect patient confidentiality and create security around protected health information. While noble in purpose, many have found it burdensome to work within the parameters set forth in the law. Physicians and patients needing legitimate access to clinical data discover endless release forms and convoluted processes standing in their way. Access to the information eventually comes in the form of reams of printed paper or faxed notes that cannot be easily consumed by or integrated into other systems.
The Meaningful Use initiative, while envisioned to improve data exchange and enhance population health, did little to help. Instead of enabling documentation efficiency and improving patient access, it promoted the proliferation of incompatible EHRs and poorly conceived patient portals. It also created heavy costs for both the federal government and physicians and was largely ineffective at producing systems whose use could be considered meaningful. The federal government paid out as much as $44,000 per physician to incentivize them to purchase medical records, while physicians often spent more than the $44,000 and, in many cases, wound up with EHRs that didn’t work well and had to be replaced.
Authors and supporters of the 21st Century Cures Act are hoping to avoid the shortcomings of prior legislation by attaching financial penalties to health care providers or IT vendors who engage in information blocking. While allowing for exceptions in appropriate cases, the law is clear: Patients deserve complete access to their medical records. While this goes against tradition, it has been proven to result in better outcomes.
Initiatives such as the OpenNotes movement have been pushing the value of full transparency for some time, and their website includes a long list of numerous examples to prove it. Indeed, several studies have demonstrated increased physician and patient satisfaction when both parties have ready access to health information. We believe that we, as physicians, should fully support the idea and lobby our EHR vendors to do the same.
It is time to tear down the impenetrable fortresses of traditional medicine, then work diligently to rebuild them with our patients safely inside.
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on Twitter @doctornotte. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
References
1. The Electronic Health Record Association blog
"A fortress not only protects those inside of it, but it also enslaves them to work.”
– Anthony T. Hincks
As physicians, we spend a great deal of time intending to do our best for the people we serve. We believe fundamentally in the idea that our patients come first, and we toil daily to exercise that belief. We also want our patients to feel they are driving their care as active participants along the journey. Yet time and time again, despite our greatest attempts, those efforts are stymied by the state of modern medicine;
Over the past 10 years, we have done a tremendous job of constructing expensive fortresses around patient information known as electronic health records (EHRs). Billions of dollars have been spent implementing, upgrading, and optimizing. In spite of this, physicians are increasingly frustrated by EHRs (and in many cases, long to return to the days of paper). It isn’t surprising, then, that patients are frustrated as well. We use terms such as “patient-centered care,” but patients feel like they are not in the center at all. Instead, they can find themselves feeling like complete outsiders, at the mercy of the medical juggernaut to make sure they have the appropriate information when they need it. There are several issues that contribute to the frustrations of physicians and patients, but two in particular warrant attention. The first is the diversity of Health IT systems and ongoing issues with EHR interoperability. The second is a provincial attitude surrounding transparency and medical record ownership. We will discuss both of these here, as well as recent legislation designed to advance both concerns.
We have written in previous columns about the many challenges of interoperability. Electronic health records, sold by different vendors, typically won’t “talk” to each other. In spite of years of maturation, issues of compatibility remain. Patient data locked inside of one EHR is not easily accessible by a physician using a different EHR. While efforts have been made to streamline information sharing, there are still many fortresses that cannot be breached.
Bridging the moat
The 21st Century Cures Act, enacted by Congress in December of 2016, seeks to define and require interoperability while addressing many other significant problems in health care. According to the legislation, true interoperability means that health IT should enable the secure exchange of electronic health information with other electronic record systems without special effort on the part of the user; the process should be seamless and shouldn’t be cumbersome for physicians or patients. It also must be fully supported by EHR vendors, but those vendors have been expressing significant concerns with the ways in which the act is being interpreted.
In a recent blog post, the HIMSS Electronic Health Record Association – a consortium of vendors including Epic, Allscripts, eClinicalWorks, as well as several others – expressed “significant concerns regarding timelines, ambiguous language, disincentives for innovation, and definitions related to information blocking.”1 This is not surprising, as the onus for improving interoperability falls squarely on their shoulders, and the work to get there is arduous. Regardless of one’s interpretation, the goal of the Cures act is clear: Arrive at true interoperability in the shortest period of time, while eliminating barriers that prevent patients from accessing their health records. In other words, it asks for the avoidance of “information blocking.”
Breaching the gate
Information blocking, as defined by the Cures Act, is “a practice by a health care provider, health IT developer, health information exchange, or health information network that … is likely to interfere with, prevent, or materially discourage access, exchange, or use of electronic health information.”2 This practice is explicitly prohibited by the legislation – and is ethically wrong – yet it continues to occur implicitly every day as it has for many years. Even if unintentional and solely because of the growing complexity of our information systems, it makes accessing health information incredibly cumbersome for patients. Even worse, attempts to improve patients’ ability to access their health records have only created additional obstacles.
HIPAA (the Health Insurance Portability and Accountability Act of 1996) was designed to protect patient confidentiality and create security around protected health information. While noble in purpose, many have found it burdensome to work within the parameters set forth in the law. Physicians and patients needing legitimate access to clinical data discover endless release forms and convoluted processes standing in their way. Access to the information eventually comes in the form of reams of printed paper or faxed notes that cannot be easily consumed by or integrated into other systems.
The Meaningful Use initiative, while envisioned to improve data exchange and enhance population health, did little to help. Instead of enabling documentation efficiency and improving patient access, it promoted the proliferation of incompatible EHRs and poorly conceived patient portals. It also created heavy costs for both the federal government and physicians and was largely ineffective at producing systems whose use could be considered meaningful. The federal government paid out as much as $44,000 per physician to incentivize them to purchase medical records, while physicians often spent more than the $44,000 and, in many cases, wound up with EHRs that didn’t work well and had to be replaced.
Authors and supporters of the 21st Century Cures Act are hoping to avoid the shortcomings of prior legislation by attaching financial penalties to health care providers or IT vendors who engage in information blocking. While allowing for exceptions in appropriate cases, the law is clear: Patients deserve complete access to their medical records. While this goes against tradition, it has been proven to result in better outcomes.
Initiatives such as the OpenNotes movement have been pushing the value of full transparency for some time, and their website includes a long list of numerous examples to prove it. Indeed, several studies have demonstrated increased physician and patient satisfaction when both parties have ready access to health information. We believe that we, as physicians, should fully support the idea and lobby our EHR vendors to do the same.
It is time to tear down the impenetrable fortresses of traditional medicine, then work diligently to rebuild them with our patients safely inside.
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on Twitter @doctornotte. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
References
1. The Electronic Health Record Association blog
"A fortress not only protects those inside of it, but it also enslaves them to work.”
– Anthony T. Hincks
As physicians, we spend a great deal of time intending to do our best for the people we serve. We believe fundamentally in the idea that our patients come first, and we toil daily to exercise that belief. We also want our patients to feel they are driving their care as active participants along the journey. Yet time and time again, despite our greatest attempts, those efforts are stymied by the state of modern medicine;
Over the past 10 years, we have done a tremendous job of constructing expensive fortresses around patient information known as electronic health records (EHRs). Billions of dollars have been spent implementing, upgrading, and optimizing. In spite of this, physicians are increasingly frustrated by EHRs (and in many cases, long to return to the days of paper). It isn’t surprising, then, that patients are frustrated as well. We use terms such as “patient-centered care,” but patients feel like they are not in the center at all. Instead, they can find themselves feeling like complete outsiders, at the mercy of the medical juggernaut to make sure they have the appropriate information when they need it. There are several issues that contribute to the frustrations of physicians and patients, but two in particular warrant attention. The first is the diversity of Health IT systems and ongoing issues with EHR interoperability. The second is a provincial attitude surrounding transparency and medical record ownership. We will discuss both of these here, as well as recent legislation designed to advance both concerns.
We have written in previous columns about the many challenges of interoperability. Electronic health records, sold by different vendors, typically won’t “talk” to each other. In spite of years of maturation, issues of compatibility remain. Patient data locked inside of one EHR is not easily accessible by a physician using a different EHR. While efforts have been made to streamline information sharing, there are still many fortresses that cannot be breached.
Bridging the moat
The 21st Century Cures Act, enacted by Congress in December of 2016, seeks to define and require interoperability while addressing many other significant problems in health care. According to the legislation, true interoperability means that health IT should enable the secure exchange of electronic health information with other electronic record systems without special effort on the part of the user; the process should be seamless and shouldn’t be cumbersome for physicians or patients. It also must be fully supported by EHR vendors, but those vendors have been expressing significant concerns with the ways in which the act is being interpreted.
In a recent blog post, the HIMSS Electronic Health Record Association – a consortium of vendors including Epic, Allscripts, eClinicalWorks, as well as several others – expressed “significant concerns regarding timelines, ambiguous language, disincentives for innovation, and definitions related to information blocking.”1 This is not surprising, as the onus for improving interoperability falls squarely on their shoulders, and the work to get there is arduous. Regardless of one’s interpretation, the goal of the Cures act is clear: Arrive at true interoperability in the shortest period of time, while eliminating barriers that prevent patients from accessing their health records. In other words, it asks for the avoidance of “information blocking.”
Breaching the gate
Information blocking, as defined by the Cures Act, is “a practice by a health care provider, health IT developer, health information exchange, or health information network that … is likely to interfere with, prevent, or materially discourage access, exchange, or use of electronic health information.”2 This practice is explicitly prohibited by the legislation – and is ethically wrong – yet it continues to occur implicitly every day as it has for many years. Even if unintentional and solely because of the growing complexity of our information systems, it makes accessing health information incredibly cumbersome for patients. Even worse, attempts to improve patients’ ability to access their health records have only created additional obstacles.
HIPAA (the Health Insurance Portability and Accountability Act of 1996) was designed to protect patient confidentiality and create security around protected health information. While noble in purpose, many have found it burdensome to work within the parameters set forth in the law. Physicians and patients needing legitimate access to clinical data discover endless release forms and convoluted processes standing in their way. Access to the information eventually comes in the form of reams of printed paper or faxed notes that cannot be easily consumed by or integrated into other systems.
The Meaningful Use initiative, while envisioned to improve data exchange and enhance population health, did little to help. Instead of enabling documentation efficiency and improving patient access, it promoted the proliferation of incompatible EHRs and poorly conceived patient portals. It also created heavy costs for both the federal government and physicians and was largely ineffective at producing systems whose use could be considered meaningful. The federal government paid out as much as $44,000 per physician to incentivize them to purchase medical records, while physicians often spent more than the $44,000 and, in many cases, wound up with EHRs that didn’t work well and had to be replaced.
Authors and supporters of the 21st Century Cures Act are hoping to avoid the shortcomings of prior legislation by attaching financial penalties to health care providers or IT vendors who engage in information blocking. While allowing for exceptions in appropriate cases, the law is clear: Patients deserve complete access to their medical records. While this goes against tradition, it has been proven to result in better outcomes.
Initiatives such as the OpenNotes movement have been pushing the value of full transparency for some time, and their website includes a long list of numerous examples to prove it. Indeed, several studies have demonstrated increased physician and patient satisfaction when both parties have ready access to health information. We believe that we, as physicians, should fully support the idea and lobby our EHR vendors to do the same.
It is time to tear down the impenetrable fortresses of traditional medicine, then work diligently to rebuild them with our patients safely inside.
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on Twitter @doctornotte. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
References
1. The Electronic Health Record Association blog
Video roundtable–Fibroids: Patient considerations in medical and surgical management
Read the article: Fibroids: Patient considerations in medical and surgical management
Moderator:
Joseph S. Sanfilippo, MD
Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh
Academic Division Director, Reproductive Endocrinology and Infertility
Magee Women’s Hospital
Pittsburgh, Pennsylvania
Participants:
Linda D. Bradley, MD
Professor of Surgery and Vice Chairman, Obstetrics, Gynecology, and Women’s Health Institute
Director, Center for Menstrual Disorders, Fibroids, & Hysteroscopic Services
Cleveland Clinic
Cleveland, Ohio
Ted L. Anderson, MD, PhD
Vice Chair, Clinical Operations and Quality Betty and Lonnie S. Burnett Professor Obstetrics & Gynecology
Director, Division of Gynecology
Vanderbilt University Medical Center
Nashville, Tennessee
Dr. Anderson reports no financial relationships relevant to this article. Dr. Bradley reports receiving grant support from Bayer and Capture-US; serving on the Scientific Advisory Panel of AbbVie, Bayer, Boston Scientific, Medtronics, and PCORI; and receiving royalties from Elsevier, UpToDate, and Wolters Kluwer. Dr. Sanfilippo reports no financial relationships relevant to this article.
Moderator:
Joseph S. Sanfilippo, MD
Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh
Academic Division Director, Reproductive Endocrinology and Infertility
Magee Women’s Hospital
Pittsburgh, Pennsylvania
Participants:
Linda D. Bradley, MD
Professor of Surgery and Vice Chairman, Obstetrics, Gynecology, and Women’s Health Institute
Director, Center for Menstrual Disorders, Fibroids, & Hysteroscopic Services
Cleveland Clinic
Cleveland, Ohio
Ted L. Anderson, MD, PhD
Vice Chair, Clinical Operations and Quality Betty and Lonnie S. Burnett Professor Obstetrics & Gynecology
Director, Division of Gynecology
Vanderbilt University Medical Center
Nashville, Tennessee
Dr. Anderson reports no financial relationships relevant to this article. Dr. Bradley reports receiving grant support from Bayer and Capture-US; serving on the Scientific Advisory Panel of AbbVie, Bayer, Boston Scientific, Medtronics, and PCORI; and receiving royalties from Elsevier, UpToDate, and Wolters Kluwer. Dr. Sanfilippo reports no financial relationships relevant to this article.
Moderator:
Joseph S. Sanfilippo, MD
Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh
Academic Division Director, Reproductive Endocrinology and Infertility
Magee Women’s Hospital
Pittsburgh, Pennsylvania
Participants:
Linda D. Bradley, MD
Professor of Surgery and Vice Chairman, Obstetrics, Gynecology, and Women’s Health Institute
Director, Center for Menstrual Disorders, Fibroids, & Hysteroscopic Services
Cleveland Clinic
Cleveland, Ohio
Ted L. Anderson, MD, PhD
Vice Chair, Clinical Operations and Quality Betty and Lonnie S. Burnett Professor Obstetrics & Gynecology
Director, Division of Gynecology
Vanderbilt University Medical Center
Nashville, Tennessee
Dr. Anderson reports no financial relationships relevant to this article. Dr. Bradley reports receiving grant support from Bayer and Capture-US; serving on the Scientific Advisory Panel of AbbVie, Bayer, Boston Scientific, Medtronics, and PCORI; and receiving royalties from Elsevier, UpToDate, and Wolters Kluwer. Dr. Sanfilippo reports no financial relationships relevant to this article.
Read the article: Fibroids: Patient considerations in medical and surgical management
Read the article: Fibroids: Patient considerations in medical and surgical management
FDA approves dupilumab for chronic rhinosinusitis with nasal polyps
The Food and Drug Administration has approved dupilumab (Dupixent) for the treatment of chronic rhinosinusitis accompanied by nasal polyps in adults.
FDA approval is based on results from a pair of studies involving 724 patients aged 18 years or older with chronic rhinosinusitis with nasal polyps who were symptomatic despite undergoing treatment with intranasal corticosteroids and who received either dupilumab or a placebo. Compared with the placebo group, patients receiving dupilumab had statistically significant reductions in nasal polyp size and nasal congestion; they also had an increased ability to smell and required less nasal polyp surgery and oral steroids.
The most commonly reported adverse events were injection-site reactions and eye and eyelid inflammation, which included redness, swelling, and itching. The drug can cause severe allergic reactions and eye problems, such as conjunctivitis or keratitis; patients should also not receive live vaccines while taking dupilumab.
“Nasal polyps can lead to loss of smell, and often patients require surgery to remove the polyps. Dupixent provides an important treatment option for patients whose nasal polyps are not adequately controlled with intranasal steroids. It also reduces the need for nasal polyp surgery and oral steroids,” said Sally Seymour, MD, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.
Find the full press release on the FDA website.
The Food and Drug Administration has approved dupilumab (Dupixent) for the treatment of chronic rhinosinusitis accompanied by nasal polyps in adults.
FDA approval is based on results from a pair of studies involving 724 patients aged 18 years or older with chronic rhinosinusitis with nasal polyps who were symptomatic despite undergoing treatment with intranasal corticosteroids and who received either dupilumab or a placebo. Compared with the placebo group, patients receiving dupilumab had statistically significant reductions in nasal polyp size and nasal congestion; they also had an increased ability to smell and required less nasal polyp surgery and oral steroids.
The most commonly reported adverse events were injection-site reactions and eye and eyelid inflammation, which included redness, swelling, and itching. The drug can cause severe allergic reactions and eye problems, such as conjunctivitis or keratitis; patients should also not receive live vaccines while taking dupilumab.
“Nasal polyps can lead to loss of smell, and often patients require surgery to remove the polyps. Dupixent provides an important treatment option for patients whose nasal polyps are not adequately controlled with intranasal steroids. It also reduces the need for nasal polyp surgery and oral steroids,” said Sally Seymour, MD, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.
Find the full press release on the FDA website.
The Food and Drug Administration has approved dupilumab (Dupixent) for the treatment of chronic rhinosinusitis accompanied by nasal polyps in adults.
FDA approval is based on results from a pair of studies involving 724 patients aged 18 years or older with chronic rhinosinusitis with nasal polyps who were symptomatic despite undergoing treatment with intranasal corticosteroids and who received either dupilumab or a placebo. Compared with the placebo group, patients receiving dupilumab had statistically significant reductions in nasal polyp size and nasal congestion; they also had an increased ability to smell and required less nasal polyp surgery and oral steroids.
The most commonly reported adverse events were injection-site reactions and eye and eyelid inflammation, which included redness, swelling, and itching. The drug can cause severe allergic reactions and eye problems, such as conjunctivitis or keratitis; patients should also not receive live vaccines while taking dupilumab.
“Nasal polyps can lead to loss of smell, and often patients require surgery to remove the polyps. Dupixent provides an important treatment option for patients whose nasal polyps are not adequately controlled with intranasal steroids. It also reduces the need for nasal polyp surgery and oral steroids,” said Sally Seymour, MD, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.
Find the full press release on the FDA website.
Almost half of Americans express doubts about vaccines
according to the American Osteopathic Association.
In a survey conducted by the Harris Poll on behalf of the AOA, 45% of the 2,007 respondents expressed a negative attitude towards vaccine safety, with online articles (16%) and past secrets/wrongdoings by the pharmaceutical industry (16%) cited as the leading causes, the AOA said.
There was no difference in negative attitude between men and women, but age, region, and parental status each had a notable effect. Doubts of vaccine safety were highest in those aged 18-34 years (55%) and lowest in those aged 65 and older (29%). Those living in the West had the highest rate at 50%, while residents of the Midwest were lowest at 39%, and the negative attitude rate was 55% for adults who had children under age 18 years and 40% for those who did not, the AOA reported.
Respondents to the survey, conducted May 28-30, 2019, also were asked to choose one of five statements that best expressed their view of vaccines, and those data paint a somewhat different picture:
- 2% said vaccines are unsafe and ineffective.
- 6% said that the side-effect risks outweigh the benefits.
- 9% said they were not sure if vaccines are safe and effective.
- 31% said that the benefits outweigh the risks.
- 51% said that vaccines are safe and effective.
Social media were another important source of doubt among respondents, but they have not been effective at countering the spread of vaccine misinformation, said psychiatrist Rachel Shmuts, DO, of Cherry Hill, N.J.
Confirmation bias makes it difficult to convince someone vaccines are safe, effective, and necessary once they believe they are not. “The number of people who believe vaccines are dangerous and refuse to get them is still relatively small. However, online support groups seem to solidify their beliefs, making them less susceptible to influence from their neighbors and real-world communities,” she said in the AOA statement.
Osteopathic family physician Paul Ehrmann, DO, said in the statement, “People know that a lot of practices won’t accept patients who don’t vaccinate, so when they find one that will, they spread the word to their community that it’s a safe place. Whether intentional or not, those doctors are often seen as endorsing anti-vaxxer beliefs.”
In 2017, his home state of Michigan, with other partners, put on a public information campaign. It has “significantly improved vaccination rates across demographics,” according to the statement.
“Beliefs are hard to change especially when they’re based in fear,” Dr. Ehrmann, of Royal Oak, Mich., said in the statement. “But, being responsible for our patients’ health and the public’s health, we can’t afford to give in to those fears. We must insist on evidence-based medicine.”
according to the American Osteopathic Association.
In a survey conducted by the Harris Poll on behalf of the AOA, 45% of the 2,007 respondents expressed a negative attitude towards vaccine safety, with online articles (16%) and past secrets/wrongdoings by the pharmaceutical industry (16%) cited as the leading causes, the AOA said.
There was no difference in negative attitude between men and women, but age, region, and parental status each had a notable effect. Doubts of vaccine safety were highest in those aged 18-34 years (55%) and lowest in those aged 65 and older (29%). Those living in the West had the highest rate at 50%, while residents of the Midwest were lowest at 39%, and the negative attitude rate was 55% for adults who had children under age 18 years and 40% for those who did not, the AOA reported.
Respondents to the survey, conducted May 28-30, 2019, also were asked to choose one of five statements that best expressed their view of vaccines, and those data paint a somewhat different picture:
- 2% said vaccines are unsafe and ineffective.
- 6% said that the side-effect risks outweigh the benefits.
- 9% said they were not sure if vaccines are safe and effective.
- 31% said that the benefits outweigh the risks.
- 51% said that vaccines are safe and effective.
Social media were another important source of doubt among respondents, but they have not been effective at countering the spread of vaccine misinformation, said psychiatrist Rachel Shmuts, DO, of Cherry Hill, N.J.
Confirmation bias makes it difficult to convince someone vaccines are safe, effective, and necessary once they believe they are not. “The number of people who believe vaccines are dangerous and refuse to get them is still relatively small. However, online support groups seem to solidify their beliefs, making them less susceptible to influence from their neighbors and real-world communities,” she said in the AOA statement.
Osteopathic family physician Paul Ehrmann, DO, said in the statement, “People know that a lot of practices won’t accept patients who don’t vaccinate, so when they find one that will, they spread the word to their community that it’s a safe place. Whether intentional or not, those doctors are often seen as endorsing anti-vaxxer beliefs.”
In 2017, his home state of Michigan, with other partners, put on a public information campaign. It has “significantly improved vaccination rates across demographics,” according to the statement.
“Beliefs are hard to change especially when they’re based in fear,” Dr. Ehrmann, of Royal Oak, Mich., said in the statement. “But, being responsible for our patients’ health and the public’s health, we can’t afford to give in to those fears. We must insist on evidence-based medicine.”
according to the American Osteopathic Association.
In a survey conducted by the Harris Poll on behalf of the AOA, 45% of the 2,007 respondents expressed a negative attitude towards vaccine safety, with online articles (16%) and past secrets/wrongdoings by the pharmaceutical industry (16%) cited as the leading causes, the AOA said.
There was no difference in negative attitude between men and women, but age, region, and parental status each had a notable effect. Doubts of vaccine safety were highest in those aged 18-34 years (55%) and lowest in those aged 65 and older (29%). Those living in the West had the highest rate at 50%, while residents of the Midwest were lowest at 39%, and the negative attitude rate was 55% for adults who had children under age 18 years and 40% for those who did not, the AOA reported.
Respondents to the survey, conducted May 28-30, 2019, also were asked to choose one of five statements that best expressed their view of vaccines, and those data paint a somewhat different picture:
- 2% said vaccines are unsafe and ineffective.
- 6% said that the side-effect risks outweigh the benefits.
- 9% said they were not sure if vaccines are safe and effective.
- 31% said that the benefits outweigh the risks.
- 51% said that vaccines are safe and effective.
Social media were another important source of doubt among respondents, but they have not been effective at countering the spread of vaccine misinformation, said psychiatrist Rachel Shmuts, DO, of Cherry Hill, N.J.
Confirmation bias makes it difficult to convince someone vaccines are safe, effective, and necessary once they believe they are not. “The number of people who believe vaccines are dangerous and refuse to get them is still relatively small. However, online support groups seem to solidify their beliefs, making them less susceptible to influence from their neighbors and real-world communities,” she said in the AOA statement.
Osteopathic family physician Paul Ehrmann, DO, said in the statement, “People know that a lot of practices won’t accept patients who don’t vaccinate, so when they find one that will, they spread the word to their community that it’s a safe place. Whether intentional or not, those doctors are often seen as endorsing anti-vaxxer beliefs.”
In 2017, his home state of Michigan, with other partners, put on a public information campaign. It has “significantly improved vaccination rates across demographics,” according to the statement.
“Beliefs are hard to change especially when they’re based in fear,” Dr. Ehrmann, of Royal Oak, Mich., said in the statement. “But, being responsible for our patients’ health and the public’s health, we can’t afford to give in to those fears. We must insist on evidence-based medicine.”
Guadecitabine offers limited advantage over other standards for high-risk AML
AMSTERDAM – For treatment-naive patients with acute myeloid leukemia (AML) who are ineligible for chemotherapy, guadecitabine offers similar efficacy to other standard treatment options until four cycles are administered, after which guadecitabine offers a slight survival advantage, based on results from the phase 3 ASTRAL-1 trial.
Complete responders also derived greater benefit from guadecitabine, a new hypomethylating agent, reported lead author Pierre Fenaux, MD, PhD, of the Hôpital Saint Louis, Paris.
With 815 patients, ASTRAL-1 was the largest global, randomized trial to compare low-intensity therapy options in this elderly, unfit population – specifically, patients who were at least 75 years old or had an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or more, Dr. Fenaux said at the annual congress of the European Hematology Association.
They were randomized in a 1:1 ratio to receive guadecitabine or one of three other treatment options: azacitidine, decitabine, or low-dose cytarabine. The coprimary endpoints of the trial were complete response rate and median overall survival. Safety measures were also investigated.
A demographic analysis showed that almost two-thirds of patients were at least 75 years old (62%), and about half had an ECOG status of 2 or 3, or bone marrow blasts. Approximately one-third of patients had poor-risk cytogenetics and a slightly higher proportion had secondary AML.
After a median follow-up of 25.5 months, patients had received, on average, five cycles of therapy. However, many patients (42%) received three or fewer cycles because of early death or disease progression. This therapy cessation rate was similar between the guadecitabine group (42.4%) and the other treatment group (40.8%).
The study failed to meet either coprimary endpoint across the entire patient population. Median overall survival was 7.10 months for guadecitabine versus 8.47 months for the other treatments, but this difference was not statistically significant (P = .73). Similarly, the complete response rate was slightly higher for guadecitabine (19.4% vs. 17.4%), but again, this finding carried a nonsignificant P value (P = .48).
The benefit offered by guadecitabine was realized only with extended treatment and in complete responders.
Patients who received a minimum of four cycles of guadecitabine had a median overall survival of 15.6 months, compared with 13.0 months for other treatments (P = .02). This benefit became more pronounced in those who received at least six cycles, which was associated with median overall survival of 19.5 months versus 14.9 months (P = .002). Complete responders also had extended survival when treated with guadecitabine, although this benefit was of a lesser magnitude (22.6 vs. 20.6 months; P = .07).
Most subgroup analyses, accounting for various clinical and genetic factors, showed no significant differences in primary outcomes between treatment arms, with one exception: TP53 mutations were associated with poor responses to guadecitabine, and a lack of the TP53 mutation predicted better responses to guadecitabine.
Adverse events were common, although most measures were not significantly different between treatment arms. For example, serious adverse events occurred in 81% and 75.5% of patients treated with guadecitabine and other options, respectively, while grade 3 or higher adverse events occurred in 91.5% of guadecitabine patients and 87.5% of patients treated with other options, but neither difference was statistically significant.
Adverse events leading to death occurred in 28.7% of patients treated with guadecitabine versus 29.8% of other patients, a nonsignificant difference. In contrast, Dr. Fenaux noted that patients treated with guadecitabine were significantly more likely to develop febrile neutropenia (33.9% vs. 26.5%), neutropenia (27.4% vs. 20.7%), and pneumonia (29.4% vs. 19.6%).
“In those patients [that received at least four cycles], there seemed to be some advantage of guadecitabine, which needs to be further explored,” Dr. Fenaux said. “But at least [this finding] suggests once more that for a hypomethylating agent to be efficacious, it requires a certain number of cycles, and whenever possible, at least 6 cycles to have full efficacy.”
The study was funded by Astex and Otsuka. The investigators reported additional relationships with Celgene, Janssen, and other companies.
SOURCE: Fenaux P et al. EHA Congress, Abstract S879.
AMSTERDAM – For treatment-naive patients with acute myeloid leukemia (AML) who are ineligible for chemotherapy, guadecitabine offers similar efficacy to other standard treatment options until four cycles are administered, after which guadecitabine offers a slight survival advantage, based on results from the phase 3 ASTRAL-1 trial.
Complete responders also derived greater benefit from guadecitabine, a new hypomethylating agent, reported lead author Pierre Fenaux, MD, PhD, of the Hôpital Saint Louis, Paris.
With 815 patients, ASTRAL-1 was the largest global, randomized trial to compare low-intensity therapy options in this elderly, unfit population – specifically, patients who were at least 75 years old or had an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or more, Dr. Fenaux said at the annual congress of the European Hematology Association.
They were randomized in a 1:1 ratio to receive guadecitabine or one of three other treatment options: azacitidine, decitabine, or low-dose cytarabine. The coprimary endpoints of the trial were complete response rate and median overall survival. Safety measures were also investigated.
A demographic analysis showed that almost two-thirds of patients were at least 75 years old (62%), and about half had an ECOG status of 2 or 3, or bone marrow blasts. Approximately one-third of patients had poor-risk cytogenetics and a slightly higher proportion had secondary AML.
After a median follow-up of 25.5 months, patients had received, on average, five cycles of therapy. However, many patients (42%) received three or fewer cycles because of early death or disease progression. This therapy cessation rate was similar between the guadecitabine group (42.4%) and the other treatment group (40.8%).
The study failed to meet either coprimary endpoint across the entire patient population. Median overall survival was 7.10 months for guadecitabine versus 8.47 months for the other treatments, but this difference was not statistically significant (P = .73). Similarly, the complete response rate was slightly higher for guadecitabine (19.4% vs. 17.4%), but again, this finding carried a nonsignificant P value (P = .48).
The benefit offered by guadecitabine was realized only with extended treatment and in complete responders.
Patients who received a minimum of four cycles of guadecitabine had a median overall survival of 15.6 months, compared with 13.0 months for other treatments (P = .02). This benefit became more pronounced in those who received at least six cycles, which was associated with median overall survival of 19.5 months versus 14.9 months (P = .002). Complete responders also had extended survival when treated with guadecitabine, although this benefit was of a lesser magnitude (22.6 vs. 20.6 months; P = .07).
Most subgroup analyses, accounting for various clinical and genetic factors, showed no significant differences in primary outcomes between treatment arms, with one exception: TP53 mutations were associated with poor responses to guadecitabine, and a lack of the TP53 mutation predicted better responses to guadecitabine.
Adverse events were common, although most measures were not significantly different between treatment arms. For example, serious adverse events occurred in 81% and 75.5% of patients treated with guadecitabine and other options, respectively, while grade 3 or higher adverse events occurred in 91.5% of guadecitabine patients and 87.5% of patients treated with other options, but neither difference was statistically significant.
Adverse events leading to death occurred in 28.7% of patients treated with guadecitabine versus 29.8% of other patients, a nonsignificant difference. In contrast, Dr. Fenaux noted that patients treated with guadecitabine were significantly more likely to develop febrile neutropenia (33.9% vs. 26.5%), neutropenia (27.4% vs. 20.7%), and pneumonia (29.4% vs. 19.6%).
“In those patients [that received at least four cycles], there seemed to be some advantage of guadecitabine, which needs to be further explored,” Dr. Fenaux said. “But at least [this finding] suggests once more that for a hypomethylating agent to be efficacious, it requires a certain number of cycles, and whenever possible, at least 6 cycles to have full efficacy.”
The study was funded by Astex and Otsuka. The investigators reported additional relationships with Celgene, Janssen, and other companies.
SOURCE: Fenaux P et al. EHA Congress, Abstract S879.
AMSTERDAM – For treatment-naive patients with acute myeloid leukemia (AML) who are ineligible for chemotherapy, guadecitabine offers similar efficacy to other standard treatment options until four cycles are administered, after which guadecitabine offers a slight survival advantage, based on results from the phase 3 ASTRAL-1 trial.
Complete responders also derived greater benefit from guadecitabine, a new hypomethylating agent, reported lead author Pierre Fenaux, MD, PhD, of the Hôpital Saint Louis, Paris.
With 815 patients, ASTRAL-1 was the largest global, randomized trial to compare low-intensity therapy options in this elderly, unfit population – specifically, patients who were at least 75 years old or had an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or more, Dr. Fenaux said at the annual congress of the European Hematology Association.
They were randomized in a 1:1 ratio to receive guadecitabine or one of three other treatment options: azacitidine, decitabine, or low-dose cytarabine. The coprimary endpoints of the trial were complete response rate and median overall survival. Safety measures were also investigated.
A demographic analysis showed that almost two-thirds of patients were at least 75 years old (62%), and about half had an ECOG status of 2 or 3, or bone marrow blasts. Approximately one-third of patients had poor-risk cytogenetics and a slightly higher proportion had secondary AML.
After a median follow-up of 25.5 months, patients had received, on average, five cycles of therapy. However, many patients (42%) received three or fewer cycles because of early death or disease progression. This therapy cessation rate was similar between the guadecitabine group (42.4%) and the other treatment group (40.8%).
The study failed to meet either coprimary endpoint across the entire patient population. Median overall survival was 7.10 months for guadecitabine versus 8.47 months for the other treatments, but this difference was not statistically significant (P = .73). Similarly, the complete response rate was slightly higher for guadecitabine (19.4% vs. 17.4%), but again, this finding carried a nonsignificant P value (P = .48).
The benefit offered by guadecitabine was realized only with extended treatment and in complete responders.
Patients who received a minimum of four cycles of guadecitabine had a median overall survival of 15.6 months, compared with 13.0 months for other treatments (P = .02). This benefit became more pronounced in those who received at least six cycles, which was associated with median overall survival of 19.5 months versus 14.9 months (P = .002). Complete responders also had extended survival when treated with guadecitabine, although this benefit was of a lesser magnitude (22.6 vs. 20.6 months; P = .07).
Most subgroup analyses, accounting for various clinical and genetic factors, showed no significant differences in primary outcomes between treatment arms, with one exception: TP53 mutations were associated with poor responses to guadecitabine, and a lack of the TP53 mutation predicted better responses to guadecitabine.
Adverse events were common, although most measures were not significantly different between treatment arms. For example, serious adverse events occurred in 81% and 75.5% of patients treated with guadecitabine and other options, respectively, while grade 3 or higher adverse events occurred in 91.5% of guadecitabine patients and 87.5% of patients treated with other options, but neither difference was statistically significant.
Adverse events leading to death occurred in 28.7% of patients treated with guadecitabine versus 29.8% of other patients, a nonsignificant difference. In contrast, Dr. Fenaux noted that patients treated with guadecitabine were significantly more likely to develop febrile neutropenia (33.9% vs. 26.5%), neutropenia (27.4% vs. 20.7%), and pneumonia (29.4% vs. 19.6%).
“In those patients [that received at least four cycles], there seemed to be some advantage of guadecitabine, which needs to be further explored,” Dr. Fenaux said. “But at least [this finding] suggests once more that for a hypomethylating agent to be efficacious, it requires a certain number of cycles, and whenever possible, at least 6 cycles to have full efficacy.”
The study was funded by Astex and Otsuka. The investigators reported additional relationships with Celgene, Janssen, and other companies.
SOURCE: Fenaux P et al. EHA Congress, Abstract S879.
REPORTING FROM EHA CONGRESS
Dr. Google, potty pot, Snoopy smells cancer
Paging Dr. Google
When something hurts, itches, or burns, to whom do you turn? Not Mom or your physician – we all turn first to Google.
Apparently, sharing symptoms with our omniscient virtual overlords is a national pastime. A recent survey found that nearly 90% of people googled their health symptoms well before going to a doctor. Maybe that’s why we keep getting targeted ads for itchy foot cream?
The survey team constructed a map that broke down the most-googled symptoms for each state. While many states’ highest search were related to cold and flu, some places had more intriguing googles.
Californians have issues with sweaty palms, and New Jerseyans are concerned about their lucid dreaming. Wisconsin seems to have an epidemic of “light-colored poop” (must be all the cheese), while South Carolina has the opposite problem – their most googled symptom is “dark green stool.”
Idaho’s biggest health concern was “symptoms of E. coli”; so, if you’re visiting the Gem State, maybe bring your own food.
Find your state here!
Smartphone skull spikes
Ever felt a little down because you’re just a regular Homo sapiens? Thanks to smartphones, you might be the next step on the evolutionary chain!
Humans have started developing external occipital protuberances – actual spikes – at the base of their skull. Spikes on your skull? How metal is that?
The spike was first observed in 1885. But there has been a rapid increase in the appearance of them, and researchers believe it’s because of smartphones.
Before you start panicking, know that the skull spike is not caused by toxic radiation from your phone. David Shahar’s team from the University of the Sunshine Coast in Australia studied thousands of x-rays. They believe that the skull spikes develop because of the constant hunched-neck position we all take as we pore over our devices for hours a day. The spike is most common in younger people – 1 in 4 people aged 18-30 years had it. This calls for a LOT more yoga.
The nose knows cancer
Just when you thought man’s best friend couldn’t get any better, they go and learn how to smell cancer.
According to a study published in the Journal of the American Osteopathic Association, researchers trained a group of beagles – noted for their superior sense of smell – to sniff out differences in blood samples from healthy patients and those with lung cancer. Snoopy and friends correctly identified the cancerous samples 97% of the time and are now learning how to identify lung, breast, and colorectal cancer using breath samples.
The researchers argued that their findings could pave the way for an over-the-counter test, similar to that used for pregnancy – but where the patient breathes into a device, and it tells them whether they’re positive for cancer or not. However, we suspect the researchers just want to give everyone a dog. There are worse ideas.
And that’s not even the only bit of olfactory-related cancer news we’ve got this week. We’re moving from lung cancer to brain tumors, as a group of researchers at Tampere University in Finland have developed an artificial nose to literally sniff out malignant tissue during surgery.
Electrosurgical resection is common during brain operations, and this process gives off smoke. The nose can detect differences in the smoke from malignant tissue and healthy tissue, allowing the surgeons to more precisely remove tumors from the brain.
No word yet as to whether the surgeons actually have to wear the nose on top of their own, but we can only hope.
Legalizing a not-so-straight flush
How many times has this happened to you? You get up early, hoping to be the first one to the sewage treatment plant so you can get the really fresh wastewater samples. But when you get there, all they have is frozen.
Or maybe you’re part of the research team that analyzed the wastewater of Tacoma, Wash., to determine marijuana usage before and after it became legal in the state. In that case, you’re used to the frozen stuff. Those scientists spent 3 years looking for THC-COOH, which is produced when the psychoactive THC in cannabis is metabolized in the human body, to determine if users were switching from the illegal to the legal market.
Turns out they did. THC-COOH in wastewater increased by 9% per quarter from December 2013 to December 2016, while sales increased by nearly 70% per quarter from Aug. 1, 2014, when legal sales went into effect, to December 2016.
“Given that wastewater represents a total population measure, these findings suggest that many established users switched very quickly from the illegal to the legal market,” team leader Dan Burgard, PhD, of the University of Puget Sound, said in a written statement. “This is the strongest statement possible regarding displacement of the illegal market.”
And the frozen samples? Over the course of the study, the investigators made 387 trips to the two sewage treatment plants. We’ll let MyNorthwest.com explain the rest: “The scientists would pick up a cooler full of frozen wastewater samples, thaw them, and analyze them using liquid chromatography and mass spectrometry.”
Mmm, frozen sewage. Who says science isn’t glamorous?
Paging Dr. Google
When something hurts, itches, or burns, to whom do you turn? Not Mom or your physician – we all turn first to Google.
Apparently, sharing symptoms with our omniscient virtual overlords is a national pastime. A recent survey found that nearly 90% of people googled their health symptoms well before going to a doctor. Maybe that’s why we keep getting targeted ads for itchy foot cream?
The survey team constructed a map that broke down the most-googled symptoms for each state. While many states’ highest search were related to cold and flu, some places had more intriguing googles.
Californians have issues with sweaty palms, and New Jerseyans are concerned about their lucid dreaming. Wisconsin seems to have an epidemic of “light-colored poop” (must be all the cheese), while South Carolina has the opposite problem – their most googled symptom is “dark green stool.”
Idaho’s biggest health concern was “symptoms of E. coli”; so, if you’re visiting the Gem State, maybe bring your own food.
Find your state here!
Smartphone skull spikes
Ever felt a little down because you’re just a regular Homo sapiens? Thanks to smartphones, you might be the next step on the evolutionary chain!
Humans have started developing external occipital protuberances – actual spikes – at the base of their skull. Spikes on your skull? How metal is that?
The spike was first observed in 1885. But there has been a rapid increase in the appearance of them, and researchers believe it’s because of smartphones.
Before you start panicking, know that the skull spike is not caused by toxic radiation from your phone. David Shahar’s team from the University of the Sunshine Coast in Australia studied thousands of x-rays. They believe that the skull spikes develop because of the constant hunched-neck position we all take as we pore over our devices for hours a day. The spike is most common in younger people – 1 in 4 people aged 18-30 years had it. This calls for a LOT more yoga.
The nose knows cancer
Just when you thought man’s best friend couldn’t get any better, they go and learn how to smell cancer.
According to a study published in the Journal of the American Osteopathic Association, researchers trained a group of beagles – noted for their superior sense of smell – to sniff out differences in blood samples from healthy patients and those with lung cancer. Snoopy and friends correctly identified the cancerous samples 97% of the time and are now learning how to identify lung, breast, and colorectal cancer using breath samples.
The researchers argued that their findings could pave the way for an over-the-counter test, similar to that used for pregnancy – but where the patient breathes into a device, and it tells them whether they’re positive for cancer or not. However, we suspect the researchers just want to give everyone a dog. There are worse ideas.
And that’s not even the only bit of olfactory-related cancer news we’ve got this week. We’re moving from lung cancer to brain tumors, as a group of researchers at Tampere University in Finland have developed an artificial nose to literally sniff out malignant tissue during surgery.
Electrosurgical resection is common during brain operations, and this process gives off smoke. The nose can detect differences in the smoke from malignant tissue and healthy tissue, allowing the surgeons to more precisely remove tumors from the brain.
No word yet as to whether the surgeons actually have to wear the nose on top of their own, but we can only hope.
Legalizing a not-so-straight flush
How many times has this happened to you? You get up early, hoping to be the first one to the sewage treatment plant so you can get the really fresh wastewater samples. But when you get there, all they have is frozen.
Or maybe you’re part of the research team that analyzed the wastewater of Tacoma, Wash., to determine marijuana usage before and after it became legal in the state. In that case, you’re used to the frozen stuff. Those scientists spent 3 years looking for THC-COOH, which is produced when the psychoactive THC in cannabis is metabolized in the human body, to determine if users were switching from the illegal to the legal market.
Turns out they did. THC-COOH in wastewater increased by 9% per quarter from December 2013 to December 2016, while sales increased by nearly 70% per quarter from Aug. 1, 2014, when legal sales went into effect, to December 2016.
“Given that wastewater represents a total population measure, these findings suggest that many established users switched very quickly from the illegal to the legal market,” team leader Dan Burgard, PhD, of the University of Puget Sound, said in a written statement. “This is the strongest statement possible regarding displacement of the illegal market.”
And the frozen samples? Over the course of the study, the investigators made 387 trips to the two sewage treatment plants. We’ll let MyNorthwest.com explain the rest: “The scientists would pick up a cooler full of frozen wastewater samples, thaw them, and analyze them using liquid chromatography and mass spectrometry.”
Mmm, frozen sewage. Who says science isn’t glamorous?
Paging Dr. Google
When something hurts, itches, or burns, to whom do you turn? Not Mom or your physician – we all turn first to Google.
Apparently, sharing symptoms with our omniscient virtual overlords is a national pastime. A recent survey found that nearly 90% of people googled their health symptoms well before going to a doctor. Maybe that’s why we keep getting targeted ads for itchy foot cream?
The survey team constructed a map that broke down the most-googled symptoms for each state. While many states’ highest search were related to cold and flu, some places had more intriguing googles.
Californians have issues with sweaty palms, and New Jerseyans are concerned about their lucid dreaming. Wisconsin seems to have an epidemic of “light-colored poop” (must be all the cheese), while South Carolina has the opposite problem – their most googled symptom is “dark green stool.”
Idaho’s biggest health concern was “symptoms of E. coli”; so, if you’re visiting the Gem State, maybe bring your own food.
Find your state here!
Smartphone skull spikes
Ever felt a little down because you’re just a regular Homo sapiens? Thanks to smartphones, you might be the next step on the evolutionary chain!
Humans have started developing external occipital protuberances – actual spikes – at the base of their skull. Spikes on your skull? How metal is that?
The spike was first observed in 1885. But there has been a rapid increase in the appearance of them, and researchers believe it’s because of smartphones.
Before you start panicking, know that the skull spike is not caused by toxic radiation from your phone. David Shahar’s team from the University of the Sunshine Coast in Australia studied thousands of x-rays. They believe that the skull spikes develop because of the constant hunched-neck position we all take as we pore over our devices for hours a day. The spike is most common in younger people – 1 in 4 people aged 18-30 years had it. This calls for a LOT more yoga.
The nose knows cancer
Just when you thought man’s best friend couldn’t get any better, they go and learn how to smell cancer.
According to a study published in the Journal of the American Osteopathic Association, researchers trained a group of beagles – noted for their superior sense of smell – to sniff out differences in blood samples from healthy patients and those with lung cancer. Snoopy and friends correctly identified the cancerous samples 97% of the time and are now learning how to identify lung, breast, and colorectal cancer using breath samples.
The researchers argued that their findings could pave the way for an over-the-counter test, similar to that used for pregnancy – but where the patient breathes into a device, and it tells them whether they’re positive for cancer or not. However, we suspect the researchers just want to give everyone a dog. There are worse ideas.
And that’s not even the only bit of olfactory-related cancer news we’ve got this week. We’re moving from lung cancer to brain tumors, as a group of researchers at Tampere University in Finland have developed an artificial nose to literally sniff out malignant tissue during surgery.
Electrosurgical resection is common during brain operations, and this process gives off smoke. The nose can detect differences in the smoke from malignant tissue and healthy tissue, allowing the surgeons to more precisely remove tumors from the brain.
No word yet as to whether the surgeons actually have to wear the nose on top of their own, but we can only hope.
Legalizing a not-so-straight flush
How many times has this happened to you? You get up early, hoping to be the first one to the sewage treatment plant so you can get the really fresh wastewater samples. But when you get there, all they have is frozen.
Or maybe you’re part of the research team that analyzed the wastewater of Tacoma, Wash., to determine marijuana usage before and after it became legal in the state. In that case, you’re used to the frozen stuff. Those scientists spent 3 years looking for THC-COOH, which is produced when the psychoactive THC in cannabis is metabolized in the human body, to determine if users were switching from the illegal to the legal market.
Turns out they did. THC-COOH in wastewater increased by 9% per quarter from December 2013 to December 2016, while sales increased by nearly 70% per quarter from Aug. 1, 2014, when legal sales went into effect, to December 2016.
“Given that wastewater represents a total population measure, these findings suggest that many established users switched very quickly from the illegal to the legal market,” team leader Dan Burgard, PhD, of the University of Puget Sound, said in a written statement. “This is the strongest statement possible regarding displacement of the illegal market.”
And the frozen samples? Over the course of the study, the investigators made 387 trips to the two sewage treatment plants. We’ll let MyNorthwest.com explain the rest: “The scientists would pick up a cooler full of frozen wastewater samples, thaw them, and analyze them using liquid chromatography and mass spectrometry.”
Mmm, frozen sewage. Who says science isn’t glamorous?
Rituximab and vemurafenib could challenge frontline chemotherapy for HCL
AMSTERDAM – A combination of rituximab and the BRAF inhibitor vemurafenib could be the one-two punch needed for relapsed or refractory hairy cell leukemia (HCL), according to investigators.
Among evaluable patients treated with this combination, 96% achieved complete remission, reported lead author, Enrico Tiacci, MD, of the University and Hospital of Perugia, Italy.
This level of efficacy is “clearly superior to historical results with either agent alone,” Dr. Tiacci said during a presentation at the annual congress of the European Hematology Association, citing previous complete response rates with vemurafenib alone of 35%-40%. “[This combination] has potential for challenging chemotherapy in the frontline setting,” he said.
The phase 2 trial involved 31 patients with relapsed or refractory HCL who had received a median of three previous therapies. Eight of the patients (26%) had primary refractory disease. Patients received vemurafenib 960 mg, twice daily for 8 weeks and rituximab 375 mg/m2, every 2 weeks. After finishing vemurafenib, patients received rituximab four more times, keeping the interval of 2 weeks. Complete remission was defined as a normal blood count, no leukemic cells in bone marrow biopsies and blood smears, and no palpable splenomegaly.
Out of 31 patients, 27 were evaluable at data cutoff. Of these, 26 (96%) achieved complete remission. The investigators noted that two complete responders had incomplete platelet recovery at the end of treatment that resolved soon after, and two patients had persistent splenomegaly, but were considered to be in complete remission at 22.5 and 25 months after finishing therapy.
All of the complete responders had previously received purine analogs, while a few had been refractory to a prior BRAF inhibitor (n = 7) and/or rituximab (n = 5).
The investigators also pointed out that 15 out of 24 evaluable patients (63%) achieved complete remission just 4 weeks after starting the trial regimen. Almost two-thirds of patients (65%) were negative for minimal residual disease (MRD). The rate of progression-free survival at a median follow-up of 29.5 months was 83%. Disease progression occurred exclusively in patients who were MRD positive.
The combination was well tolerated; most adverse events were of grade 1 or 2, overlapping with the safety profile of each agent alone.
Reflecting on the study findings, Dr. Tiacci suggested that the combination could be most effective if delivered immediately, instead of after BRAF failure.
“Interestingly,” he said, “the relapse-free survival in patients naive to a BRAF inhibitor remained significantly longer than the relapse-free interval that patients previously exposed to a BRAF inhibitor enjoyed, both following monotherapy with a BRAF inhibitor and following subsequent combination with rituximab, potentially suggesting that vemurafenib should be used directly in combination with rituximab rather than being delivered first as a monotherapy and then added to rituximab at relapse.”
Randomized testing of the combination against the chemotherapy-based standard of care in the frontline setting is warranted, the investigators concluded.
Dr. Tiacci reported financial relationships with Roche, AbbVie, and Shire.
SOURCE: Tiacci E et al. EHA Congress, Abstract S104.
AMSTERDAM – A combination of rituximab and the BRAF inhibitor vemurafenib could be the one-two punch needed for relapsed or refractory hairy cell leukemia (HCL), according to investigators.
Among evaluable patients treated with this combination, 96% achieved complete remission, reported lead author, Enrico Tiacci, MD, of the University and Hospital of Perugia, Italy.
This level of efficacy is “clearly superior to historical results with either agent alone,” Dr. Tiacci said during a presentation at the annual congress of the European Hematology Association, citing previous complete response rates with vemurafenib alone of 35%-40%. “[This combination] has potential for challenging chemotherapy in the frontline setting,” he said.
The phase 2 trial involved 31 patients with relapsed or refractory HCL who had received a median of three previous therapies. Eight of the patients (26%) had primary refractory disease. Patients received vemurafenib 960 mg, twice daily for 8 weeks and rituximab 375 mg/m2, every 2 weeks. After finishing vemurafenib, patients received rituximab four more times, keeping the interval of 2 weeks. Complete remission was defined as a normal blood count, no leukemic cells in bone marrow biopsies and blood smears, and no palpable splenomegaly.
Out of 31 patients, 27 were evaluable at data cutoff. Of these, 26 (96%) achieved complete remission. The investigators noted that two complete responders had incomplete platelet recovery at the end of treatment that resolved soon after, and two patients had persistent splenomegaly, but were considered to be in complete remission at 22.5 and 25 months after finishing therapy.
All of the complete responders had previously received purine analogs, while a few had been refractory to a prior BRAF inhibitor (n = 7) and/or rituximab (n = 5).
The investigators also pointed out that 15 out of 24 evaluable patients (63%) achieved complete remission just 4 weeks after starting the trial regimen. Almost two-thirds of patients (65%) were negative for minimal residual disease (MRD). The rate of progression-free survival at a median follow-up of 29.5 months was 83%. Disease progression occurred exclusively in patients who were MRD positive.
The combination was well tolerated; most adverse events were of grade 1 or 2, overlapping with the safety profile of each agent alone.
Reflecting on the study findings, Dr. Tiacci suggested that the combination could be most effective if delivered immediately, instead of after BRAF failure.
“Interestingly,” he said, “the relapse-free survival in patients naive to a BRAF inhibitor remained significantly longer than the relapse-free interval that patients previously exposed to a BRAF inhibitor enjoyed, both following monotherapy with a BRAF inhibitor and following subsequent combination with rituximab, potentially suggesting that vemurafenib should be used directly in combination with rituximab rather than being delivered first as a monotherapy and then added to rituximab at relapse.”
Randomized testing of the combination against the chemotherapy-based standard of care in the frontline setting is warranted, the investigators concluded.
Dr. Tiacci reported financial relationships with Roche, AbbVie, and Shire.
SOURCE: Tiacci E et al. EHA Congress, Abstract S104.
AMSTERDAM – A combination of rituximab and the BRAF inhibitor vemurafenib could be the one-two punch needed for relapsed or refractory hairy cell leukemia (HCL), according to investigators.
Among evaluable patients treated with this combination, 96% achieved complete remission, reported lead author, Enrico Tiacci, MD, of the University and Hospital of Perugia, Italy.
This level of efficacy is “clearly superior to historical results with either agent alone,” Dr. Tiacci said during a presentation at the annual congress of the European Hematology Association, citing previous complete response rates with vemurafenib alone of 35%-40%. “[This combination] has potential for challenging chemotherapy in the frontline setting,” he said.
The phase 2 trial involved 31 patients with relapsed or refractory HCL who had received a median of three previous therapies. Eight of the patients (26%) had primary refractory disease. Patients received vemurafenib 960 mg, twice daily for 8 weeks and rituximab 375 mg/m2, every 2 weeks. After finishing vemurafenib, patients received rituximab four more times, keeping the interval of 2 weeks. Complete remission was defined as a normal blood count, no leukemic cells in bone marrow biopsies and blood smears, and no palpable splenomegaly.
Out of 31 patients, 27 were evaluable at data cutoff. Of these, 26 (96%) achieved complete remission. The investigators noted that two complete responders had incomplete platelet recovery at the end of treatment that resolved soon after, and two patients had persistent splenomegaly, but were considered to be in complete remission at 22.5 and 25 months after finishing therapy.
All of the complete responders had previously received purine analogs, while a few had been refractory to a prior BRAF inhibitor (n = 7) and/or rituximab (n = 5).
The investigators also pointed out that 15 out of 24 evaluable patients (63%) achieved complete remission just 4 weeks after starting the trial regimen. Almost two-thirds of patients (65%) were negative for minimal residual disease (MRD). The rate of progression-free survival at a median follow-up of 29.5 months was 83%. Disease progression occurred exclusively in patients who were MRD positive.
The combination was well tolerated; most adverse events were of grade 1 or 2, overlapping with the safety profile of each agent alone.
Reflecting on the study findings, Dr. Tiacci suggested that the combination could be most effective if delivered immediately, instead of after BRAF failure.
“Interestingly,” he said, “the relapse-free survival in patients naive to a BRAF inhibitor remained significantly longer than the relapse-free interval that patients previously exposed to a BRAF inhibitor enjoyed, both following monotherapy with a BRAF inhibitor and following subsequent combination with rituximab, potentially suggesting that vemurafenib should be used directly in combination with rituximab rather than being delivered first as a monotherapy and then added to rituximab at relapse.”
Randomized testing of the combination against the chemotherapy-based standard of care in the frontline setting is warranted, the investigators concluded.
Dr. Tiacci reported financial relationships with Roche, AbbVie, and Shire.
SOURCE: Tiacci E et al. EHA Congress, Abstract S104.
REPORTING FROM EHA CONGRESS