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Cancer incidence has increased in patients under age 50
Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.
Early-onset cancer
Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.
Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
Increase in deaths
There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.
The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.
“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
Industrialized countries
The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.
In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.
On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
Hypotheses and limitations
How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.
The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.
For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”
They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”
The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
Trend in the United States
Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.
In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.
Early-onset cancer
Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.
Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
Increase in deaths
There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.
The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.
“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
Industrialized countries
The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.
In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.
On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
Hypotheses and limitations
How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.
The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.
For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”
They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”
The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
Trend in the United States
Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.
In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.
Early-onset cancer
Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.
Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
Increase in deaths
There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.
The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.
“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
Industrialized countries
The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.
In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.
On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
Hypotheses and limitations
How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.
The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.
For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”
They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”
The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
Trend in the United States
Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.
In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
from bmj oncology
Therapeutic vaccine shows promise in treating lung cancer
SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer,
The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.
The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.
Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
Study protocol
In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.
In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
Secondary resistance
The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.
“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.
Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.
Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.
For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.
“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
Tolerability profile
Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).
The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.
“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
Clinical development
The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.
Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.
The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.
OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.
The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer,
The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.
The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.
Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
Study protocol
In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.
In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
Secondary resistance
The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.
“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.
Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.
Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.
For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.
“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
Tolerability profile
Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).
The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.
“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
Clinical development
The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.
Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.
The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.
OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.
The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer,
The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.
The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.
Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
Study protocol
In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.
In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
Secondary resistance
The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.
“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.
Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.
Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.
For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.
“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
Tolerability profile
Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).
The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.
“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
Clinical development
The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.
Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.
The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.
OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.
The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
AT WCLC 2023
New antibiotic could combat multidrug-resistant superbugs
Antibiotic resistance is a major public health problem. Few new molecules are in development, but a new antibiotic called clovibactin brings hope.
The drug was discovered and has been studied by scientists from Utrecht University in the Netherlands, the University of Bonn in Germany, the German Center for Infection Research, Northeastern University in Boston, and NovoBiotic Pharmaceuticals in Cambridge, Mass.
Their research was published in Cell.
“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” Markus Weingarth, MD, PhD, a researcher in Utrecht University’s chemistry department, said in a press release.
Microbial “dark matter”
Researchers isolated clovibactin from sandy soil from North Carolina and studied it using the iChip device, which was developed in 2015. This technique allowed them to grow “bacterial dark matter,” so-called unculturable bacteria, which compose a group to which 99% of bacteria belong.
This device also paved the way for the discovery of the antibiotic teixobactin in 2020. Teixobactin is effective against gram-positive bacteria and is one of the first truly new antibiotics in decades. Its mechanism of action is like that of clovibactin.
Combats resistant bacteria
In the Cell article, the researchers showed that clovibactin acts via several mechanisms and that it successfully treated mice infected with the superbug Staphylococcus aureus.
Clovibactin exhibited antibacterial activity against a broad range of gram-positive pathogens, including methicillin-resistant S. aureus, daptomycin-resistant and vancomycin-resistant S. aureus strains, and difficult-to-treat vancomycin-resistant Enterococcus faecalis and E faecium (vancomycin-resistant enterococci). Escherichia coli was only marginally affected “compared with an outer membrane deficient E. coli WO153 strain, probably reflecting insufficient penetration of the compound,” the authors wrote.
Original mechanism of action
Clovibactin acts not on one but three molecules, all of which are essential to the construction of bacterial walls: C55PP, lipid II, and lipid IIIWTA, which are from different cell wall biosynthetic pathways. Clovibactin binds to the pyrophosphate portion of these precursors.
“Clovibactin wraps around the pyrophosphate like [a] tight glove, like a cage that encloses its target,” said Dr. Weingarth. This is what gives clovibactin its name, which is derived from Greek word klouvi, meaning cage.
The remarkable aspect of clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it also ignores the variable sugar-peptide part of the targets. The bacteria therefore have a much harder time developing resistance against it. “In fact, we did not observe any resistance to clovibactin in our studies,” Dr. Weingarth confirmed.
Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.
Few side effects
Because of the mechanism of action of the antibiotic, few side effects are predicted. Indeed, clovibactin targets bacteria cells but not human cells.
“Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why clovibactin selectively damages bacterial cells but is not toxic to human cells,” said Dr. Weingarth.
Other studies – in particular, studies in humans – are needed before the antibiotic can be considered a potential treatment. In the meantime, regulations regarding the proper use of antibiotics must continue to be applied to limit antibiotic resistance.
In 2019, 4.95 million deaths worldwide were associated with bacterial antimicrobial resistance, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance. If this trend continues without new medicines becoming available to treat bacterial infections, it is estimated that by 2050, 10 million people will die every year from antimicrobial drug resistance.
This article was translated from the Medscape French Edition. A version appeared on Medscape.com.
Antibiotic resistance is a major public health problem. Few new molecules are in development, but a new antibiotic called clovibactin brings hope.
The drug was discovered and has been studied by scientists from Utrecht University in the Netherlands, the University of Bonn in Germany, the German Center for Infection Research, Northeastern University in Boston, and NovoBiotic Pharmaceuticals in Cambridge, Mass.
Their research was published in Cell.
“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” Markus Weingarth, MD, PhD, a researcher in Utrecht University’s chemistry department, said in a press release.
Microbial “dark matter”
Researchers isolated clovibactin from sandy soil from North Carolina and studied it using the iChip device, which was developed in 2015. This technique allowed them to grow “bacterial dark matter,” so-called unculturable bacteria, which compose a group to which 99% of bacteria belong.
This device also paved the way for the discovery of the antibiotic teixobactin in 2020. Teixobactin is effective against gram-positive bacteria and is one of the first truly new antibiotics in decades. Its mechanism of action is like that of clovibactin.
Combats resistant bacteria
In the Cell article, the researchers showed that clovibactin acts via several mechanisms and that it successfully treated mice infected with the superbug Staphylococcus aureus.
Clovibactin exhibited antibacterial activity against a broad range of gram-positive pathogens, including methicillin-resistant S. aureus, daptomycin-resistant and vancomycin-resistant S. aureus strains, and difficult-to-treat vancomycin-resistant Enterococcus faecalis and E faecium (vancomycin-resistant enterococci). Escherichia coli was only marginally affected “compared with an outer membrane deficient E. coli WO153 strain, probably reflecting insufficient penetration of the compound,” the authors wrote.
Original mechanism of action
Clovibactin acts not on one but three molecules, all of which are essential to the construction of bacterial walls: C55PP, lipid II, and lipid IIIWTA, which are from different cell wall biosynthetic pathways. Clovibactin binds to the pyrophosphate portion of these precursors.
“Clovibactin wraps around the pyrophosphate like [a] tight glove, like a cage that encloses its target,” said Dr. Weingarth. This is what gives clovibactin its name, which is derived from Greek word klouvi, meaning cage.
The remarkable aspect of clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it also ignores the variable sugar-peptide part of the targets. The bacteria therefore have a much harder time developing resistance against it. “In fact, we did not observe any resistance to clovibactin in our studies,” Dr. Weingarth confirmed.
Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.
Few side effects
Because of the mechanism of action of the antibiotic, few side effects are predicted. Indeed, clovibactin targets bacteria cells but not human cells.
“Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why clovibactin selectively damages bacterial cells but is not toxic to human cells,” said Dr. Weingarth.
Other studies – in particular, studies in humans – are needed before the antibiotic can be considered a potential treatment. In the meantime, regulations regarding the proper use of antibiotics must continue to be applied to limit antibiotic resistance.
In 2019, 4.95 million deaths worldwide were associated with bacterial antimicrobial resistance, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance. If this trend continues without new medicines becoming available to treat bacterial infections, it is estimated that by 2050, 10 million people will die every year from antimicrobial drug resistance.
This article was translated from the Medscape French Edition. A version appeared on Medscape.com.
Antibiotic resistance is a major public health problem. Few new molecules are in development, but a new antibiotic called clovibactin brings hope.
The drug was discovered and has been studied by scientists from Utrecht University in the Netherlands, the University of Bonn in Germany, the German Center for Infection Research, Northeastern University in Boston, and NovoBiotic Pharmaceuticals in Cambridge, Mass.
Their research was published in Cell.
“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” Markus Weingarth, MD, PhD, a researcher in Utrecht University’s chemistry department, said in a press release.
Microbial “dark matter”
Researchers isolated clovibactin from sandy soil from North Carolina and studied it using the iChip device, which was developed in 2015. This technique allowed them to grow “bacterial dark matter,” so-called unculturable bacteria, which compose a group to which 99% of bacteria belong.
This device also paved the way for the discovery of the antibiotic teixobactin in 2020. Teixobactin is effective against gram-positive bacteria and is one of the first truly new antibiotics in decades. Its mechanism of action is like that of clovibactin.
Combats resistant bacteria
In the Cell article, the researchers showed that clovibactin acts via several mechanisms and that it successfully treated mice infected with the superbug Staphylococcus aureus.
Clovibactin exhibited antibacterial activity against a broad range of gram-positive pathogens, including methicillin-resistant S. aureus, daptomycin-resistant and vancomycin-resistant S. aureus strains, and difficult-to-treat vancomycin-resistant Enterococcus faecalis and E faecium (vancomycin-resistant enterococci). Escherichia coli was only marginally affected “compared with an outer membrane deficient E. coli WO153 strain, probably reflecting insufficient penetration of the compound,” the authors wrote.
Original mechanism of action
Clovibactin acts not on one but three molecules, all of which are essential to the construction of bacterial walls: C55PP, lipid II, and lipid IIIWTA, which are from different cell wall biosynthetic pathways. Clovibactin binds to the pyrophosphate portion of these precursors.
“Clovibactin wraps around the pyrophosphate like [a] tight glove, like a cage that encloses its target,” said Dr. Weingarth. This is what gives clovibactin its name, which is derived from Greek word klouvi, meaning cage.
The remarkable aspect of clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it also ignores the variable sugar-peptide part of the targets. The bacteria therefore have a much harder time developing resistance against it. “In fact, we did not observe any resistance to clovibactin in our studies,” Dr. Weingarth confirmed.
Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.
Few side effects
Because of the mechanism of action of the antibiotic, few side effects are predicted. Indeed, clovibactin targets bacteria cells but not human cells.
“Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why clovibactin selectively damages bacterial cells but is not toxic to human cells,” said Dr. Weingarth.
Other studies – in particular, studies in humans – are needed before the antibiotic can be considered a potential treatment. In the meantime, regulations regarding the proper use of antibiotics must continue to be applied to limit antibiotic resistance.
In 2019, 4.95 million deaths worldwide were associated with bacterial antimicrobial resistance, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance. If this trend continues without new medicines becoming available to treat bacterial infections, it is estimated that by 2050, 10 million people will die every year from antimicrobial drug resistance.
This article was translated from the Medscape French Edition. A version appeared on Medscape.com.
FROM CELL
Do the data support psychedelics in addiction therapy?
PARIS – “We need to develop new therapies to treat addiction because of the related cost to society, which is extremely high,” said Bruno Roméo, MD, psychiatrist and addiction specialist at Paul Brousse Hospital in Villejuif, France, at the Paris-based Neuroscience, Psychiatry and Neurology Conference. Dr. Roméo spoke about the current place of psychedelics in the treatment of addiction.
“Smoking and alcohol consumption are the two main preventable causes of death in France,” he said. “Current management strategies for these addictions rarely involve pharmacological therapies, which are not very effective, in any case. We have massive relapse rates, signaling the need to develop other treatments, like psychedelic drugs.”
But what data are available on the efficacy of psychedelics in treating addiction?
Alcohol use disorder
There are few data concerning the role of psychedelics in the treatment of alcohol use disorder, but one controlled, randomized trial evaluated the efficacy of psilocybin. That trial was published in JAMA Psychiatry in 2022.
That study included 95 patients with alcohol use disorder; 49 were treated with psilocybin, and 46 were treated with diphenhydramine.
An initial medication session of psilocybin was given in week 4, then another in week 8 at a higher dose. The number of drinking days, the number of heavy drinking days, and the number of drinks consumed between weeks 32 and 36 were assessed.
The investigators showed that, after two sessions with psilocybin, there was a significant reduction in the number of heavy drinking days. In the control group, between weeks 5 and 36, 20% of days involved heavy drinking, whereas in the psilocybin group, 10% of days involved heavy drinking.
There was also a significant and rapid reduction in the number of drinking days, and this was maintained over time. Between weeks 5 and 36, just over 40% of days were reported as drinking days in the control group versus slightly more than 30% in the psilocybin group.
Similarly, the number of glasses per day was drastically reduced after taking psilocybin, and the effect occurred extremely quickly. Consumption went from six drinks to less than one drink between weeks 5 and 8. Overall, between weeks 5 and 36, the number of drinks consumed per day was more than two in the placebo group and more than one in the psilocybin group.
“Psilocybin was seen as having potential efficacy in treating alcohol use disorder. But we must tread carefully with these results; the profile of the patients enrolled in this study is different to that of the patients we regularly see in our addiction clinics. The patients enrolled in the study reported less than 60% of days as heavy drinking days,” said Dr. Romeo.
Candidates for psilocybin
According to a retrospective survey of 160 respondents that was conducted online at Paul Brousse Hospital, patients with the most severe cases of alcohol use disorder who have the most mystical psychedelic experiences seem to respond best to psilocybin and to reduce their alcohol use. It also appears that patients whose alcohol use decreased the most had lower psychological flexibility on enrollment in the study. (Psychological flexibility is the ability to adapt to change and to cope with positive and negative experiences in real time without being fazed or trying to flee from the situation.) “It’s as if they had a broader capacity for change, and psychedelics helped them more,” said Dr. Roméo.
Smoking cessation
“There are even fewer studies for smoking,” said Dr. Roméo. In a pilot study with 15 patients, the researchers gave two or three doses of psilocybin at 20-30 mg in combination with cognitive-behavioral therapy one session per week for 10 weeks. Thereafter, patients were assessed three times: after 6 months, 12 months, and 30 months.
The results showed a significant reduction in smoking. Patients went from smoking more than 15 cigarettes per day to smoking one to two cigarettes per day before going back up to six cigarettes daily.
Regarding abstinence rates, 12 of 15 patients had stopped smoking after 6 months, 8 of 15 after 1 year, and 7 of 15 after 30 months. “This study produced some interesting results, although caution must obviously be taken due to the very low number of patients enrolled,” said Dr. Roméo.
As is the case for alcohol, a retrospective survey conducted via questionnaire at Paul Brousse Hospital showed that the patients who smoked the most and who had the most mystical psychedelic experiences seemed to respond best to psilocybin and therefore to reduce their tobacco use. It also seemed to be the case that patients who reduced tobacco use the most had lower psychological flexibility on enrollment in the study.
Constraints on psychedelics
“Psychedelics are somewhat effective in treating addiction, but there are various limitations to their use,” said Dr. Roméo.
One of those limitations is societal. Laurence Bézo, MD, of the addiction services clinic at Paul Brousse Hospital, asked doctors to respond to a questionnaire to determine what they thought about psychedelics. To date, 407 have responded, including 280 general practitioners, 50 addiction specialists, and 50 specialist physicians. Overall, 50% think that psychedelics have no therapeutic potential. Three of five doctors also said that psychedelics are dangerous. Just over half thought that their use is associated with a severe risk of aggression aimed at oneself and toward others. Likewise, half think that the risk of dependency is very high and that there is a risk of co-occurring psychiatric disorders. “From the pool of physicians queried, the consensus is that psychedelics are pretty dangerous. People also seem to frown upon prescribing psychedelics in France,” said Dr. Roméo.
Participants went as far as to classify psychedelics as some of the most dangerous drugs out there.
Using a 7-point scale, they classified psychedelics below heroin and cocaine in terms of dangerousness. They are deemed much more harmful than alcohol, tobacco, and cannabis.
“A survey of the public carried out several years ago by leading French market research group IFOP had the exact same findings. Nevertheless, a number of studies have set out to determine how dangerous psychedelics are, and their findings point to this class of drugs as being among the least harmful for the individual patient and those around them. On the contrary, alcohol, heroin, crack cocaine (or even cocaine),methamphetamine, and tobacco were shown to be the most harmful. Additionally, psychedelics have a very low risk of dependency and the lowest risk of lethality. There is complete dissonance between what recent studies show us and what society, and some doctors, think,” said Dr. Roméo.
Besides these assumptions, another constraint to the use of psychedelics relates to methods adopted in related clinical studies. “Due to the effect psychedelics have, in the trials conducted, 9 participants and 9 doctors out of 10 are aware of what they have taken or given, respectively. This is a very important limitation. Nowadays, researchers don’t know how to conduct accurate double-blind studies,” said Dr. Roméo.
In sum, for psychiatrists, psychedelics are promising in addiction therapy, but health care professionals, public authorities, and society as a whole must be better informed about their use, and received ideas must be dispelled.
“The findings need to be replicated, but overall, psychedelics are really quite promising in treating both alcohol and tobacco use disorder. They are generally well tolerated with few serious side effects. There is no deterioration in patients with psychiatric conditions while they are taking psychedelics. And if persistent symptoms of psychosis do occur, which is extremely rare, it’s probably because there are preexisting underlying issues at play. We also don’t see increased blood pressure or any other serious physical anomalies. In a supervised setting, as is the case with studies involving psychotherapeutic support, we can no longer say, in this day and age, that psychedelics are harmful,” said Dr. Roméo.
Dr. Roméo reported no conflicts of interest regarding the content of this article.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
PARIS – “We need to develop new therapies to treat addiction because of the related cost to society, which is extremely high,” said Bruno Roméo, MD, psychiatrist and addiction specialist at Paul Brousse Hospital in Villejuif, France, at the Paris-based Neuroscience, Psychiatry and Neurology Conference. Dr. Roméo spoke about the current place of psychedelics in the treatment of addiction.
“Smoking and alcohol consumption are the two main preventable causes of death in France,” he said. “Current management strategies for these addictions rarely involve pharmacological therapies, which are not very effective, in any case. We have massive relapse rates, signaling the need to develop other treatments, like psychedelic drugs.”
But what data are available on the efficacy of psychedelics in treating addiction?
Alcohol use disorder
There are few data concerning the role of psychedelics in the treatment of alcohol use disorder, but one controlled, randomized trial evaluated the efficacy of psilocybin. That trial was published in JAMA Psychiatry in 2022.
That study included 95 patients with alcohol use disorder; 49 were treated with psilocybin, and 46 were treated with diphenhydramine.
An initial medication session of psilocybin was given in week 4, then another in week 8 at a higher dose. The number of drinking days, the number of heavy drinking days, and the number of drinks consumed between weeks 32 and 36 were assessed.
The investigators showed that, after two sessions with psilocybin, there was a significant reduction in the number of heavy drinking days. In the control group, between weeks 5 and 36, 20% of days involved heavy drinking, whereas in the psilocybin group, 10% of days involved heavy drinking.
There was also a significant and rapid reduction in the number of drinking days, and this was maintained over time. Between weeks 5 and 36, just over 40% of days were reported as drinking days in the control group versus slightly more than 30% in the psilocybin group.
Similarly, the number of glasses per day was drastically reduced after taking psilocybin, and the effect occurred extremely quickly. Consumption went from six drinks to less than one drink between weeks 5 and 8. Overall, between weeks 5 and 36, the number of drinks consumed per day was more than two in the placebo group and more than one in the psilocybin group.
“Psilocybin was seen as having potential efficacy in treating alcohol use disorder. But we must tread carefully with these results; the profile of the patients enrolled in this study is different to that of the patients we regularly see in our addiction clinics. The patients enrolled in the study reported less than 60% of days as heavy drinking days,” said Dr. Romeo.
Candidates for psilocybin
According to a retrospective survey of 160 respondents that was conducted online at Paul Brousse Hospital, patients with the most severe cases of alcohol use disorder who have the most mystical psychedelic experiences seem to respond best to psilocybin and to reduce their alcohol use. It also appears that patients whose alcohol use decreased the most had lower psychological flexibility on enrollment in the study. (Psychological flexibility is the ability to adapt to change and to cope with positive and negative experiences in real time without being fazed or trying to flee from the situation.) “It’s as if they had a broader capacity for change, and psychedelics helped them more,” said Dr. Roméo.
Smoking cessation
“There are even fewer studies for smoking,” said Dr. Roméo. In a pilot study with 15 patients, the researchers gave two or three doses of psilocybin at 20-30 mg in combination with cognitive-behavioral therapy one session per week for 10 weeks. Thereafter, patients were assessed three times: after 6 months, 12 months, and 30 months.
The results showed a significant reduction in smoking. Patients went from smoking more than 15 cigarettes per day to smoking one to two cigarettes per day before going back up to six cigarettes daily.
Regarding abstinence rates, 12 of 15 patients had stopped smoking after 6 months, 8 of 15 after 1 year, and 7 of 15 after 30 months. “This study produced some interesting results, although caution must obviously be taken due to the very low number of patients enrolled,” said Dr. Roméo.
As is the case for alcohol, a retrospective survey conducted via questionnaire at Paul Brousse Hospital showed that the patients who smoked the most and who had the most mystical psychedelic experiences seemed to respond best to psilocybin and therefore to reduce their tobacco use. It also seemed to be the case that patients who reduced tobacco use the most had lower psychological flexibility on enrollment in the study.
Constraints on psychedelics
“Psychedelics are somewhat effective in treating addiction, but there are various limitations to their use,” said Dr. Roméo.
One of those limitations is societal. Laurence Bézo, MD, of the addiction services clinic at Paul Brousse Hospital, asked doctors to respond to a questionnaire to determine what they thought about psychedelics. To date, 407 have responded, including 280 general practitioners, 50 addiction specialists, and 50 specialist physicians. Overall, 50% think that psychedelics have no therapeutic potential. Three of five doctors also said that psychedelics are dangerous. Just over half thought that their use is associated with a severe risk of aggression aimed at oneself and toward others. Likewise, half think that the risk of dependency is very high and that there is a risk of co-occurring psychiatric disorders. “From the pool of physicians queried, the consensus is that psychedelics are pretty dangerous. People also seem to frown upon prescribing psychedelics in France,” said Dr. Roméo.
Participants went as far as to classify psychedelics as some of the most dangerous drugs out there.
Using a 7-point scale, they classified psychedelics below heroin and cocaine in terms of dangerousness. They are deemed much more harmful than alcohol, tobacco, and cannabis.
“A survey of the public carried out several years ago by leading French market research group IFOP had the exact same findings. Nevertheless, a number of studies have set out to determine how dangerous psychedelics are, and their findings point to this class of drugs as being among the least harmful for the individual patient and those around them. On the contrary, alcohol, heroin, crack cocaine (or even cocaine),methamphetamine, and tobacco were shown to be the most harmful. Additionally, psychedelics have a very low risk of dependency and the lowest risk of lethality. There is complete dissonance between what recent studies show us and what society, and some doctors, think,” said Dr. Roméo.
Besides these assumptions, another constraint to the use of psychedelics relates to methods adopted in related clinical studies. “Due to the effect psychedelics have, in the trials conducted, 9 participants and 9 doctors out of 10 are aware of what they have taken or given, respectively. This is a very important limitation. Nowadays, researchers don’t know how to conduct accurate double-blind studies,” said Dr. Roméo.
In sum, for psychiatrists, psychedelics are promising in addiction therapy, but health care professionals, public authorities, and society as a whole must be better informed about their use, and received ideas must be dispelled.
“The findings need to be replicated, but overall, psychedelics are really quite promising in treating both alcohol and tobacco use disorder. They are generally well tolerated with few serious side effects. There is no deterioration in patients with psychiatric conditions while they are taking psychedelics. And if persistent symptoms of psychosis do occur, which is extremely rare, it’s probably because there are preexisting underlying issues at play. We also don’t see increased blood pressure or any other serious physical anomalies. In a supervised setting, as is the case with studies involving psychotherapeutic support, we can no longer say, in this day and age, that psychedelics are harmful,” said Dr. Roméo.
Dr. Roméo reported no conflicts of interest regarding the content of this article.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
PARIS – “We need to develop new therapies to treat addiction because of the related cost to society, which is extremely high,” said Bruno Roméo, MD, psychiatrist and addiction specialist at Paul Brousse Hospital in Villejuif, France, at the Paris-based Neuroscience, Psychiatry and Neurology Conference. Dr. Roméo spoke about the current place of psychedelics in the treatment of addiction.
“Smoking and alcohol consumption are the two main preventable causes of death in France,” he said. “Current management strategies for these addictions rarely involve pharmacological therapies, which are not very effective, in any case. We have massive relapse rates, signaling the need to develop other treatments, like psychedelic drugs.”
But what data are available on the efficacy of psychedelics in treating addiction?
Alcohol use disorder
There are few data concerning the role of psychedelics in the treatment of alcohol use disorder, but one controlled, randomized trial evaluated the efficacy of psilocybin. That trial was published in JAMA Psychiatry in 2022.
That study included 95 patients with alcohol use disorder; 49 were treated with psilocybin, and 46 were treated with diphenhydramine.
An initial medication session of psilocybin was given in week 4, then another in week 8 at a higher dose. The number of drinking days, the number of heavy drinking days, and the number of drinks consumed between weeks 32 and 36 were assessed.
The investigators showed that, after two sessions with psilocybin, there was a significant reduction in the number of heavy drinking days. In the control group, between weeks 5 and 36, 20% of days involved heavy drinking, whereas in the psilocybin group, 10% of days involved heavy drinking.
There was also a significant and rapid reduction in the number of drinking days, and this was maintained over time. Between weeks 5 and 36, just over 40% of days were reported as drinking days in the control group versus slightly more than 30% in the psilocybin group.
Similarly, the number of glasses per day was drastically reduced after taking psilocybin, and the effect occurred extremely quickly. Consumption went from six drinks to less than one drink between weeks 5 and 8. Overall, between weeks 5 and 36, the number of drinks consumed per day was more than two in the placebo group and more than one in the psilocybin group.
“Psilocybin was seen as having potential efficacy in treating alcohol use disorder. But we must tread carefully with these results; the profile of the patients enrolled in this study is different to that of the patients we regularly see in our addiction clinics. The patients enrolled in the study reported less than 60% of days as heavy drinking days,” said Dr. Romeo.
Candidates for psilocybin
According to a retrospective survey of 160 respondents that was conducted online at Paul Brousse Hospital, patients with the most severe cases of alcohol use disorder who have the most mystical psychedelic experiences seem to respond best to psilocybin and to reduce their alcohol use. It also appears that patients whose alcohol use decreased the most had lower psychological flexibility on enrollment in the study. (Psychological flexibility is the ability to adapt to change and to cope with positive and negative experiences in real time without being fazed or trying to flee from the situation.) “It’s as if they had a broader capacity for change, and psychedelics helped them more,” said Dr. Roméo.
Smoking cessation
“There are even fewer studies for smoking,” said Dr. Roméo. In a pilot study with 15 patients, the researchers gave two or three doses of psilocybin at 20-30 mg in combination with cognitive-behavioral therapy one session per week for 10 weeks. Thereafter, patients were assessed three times: after 6 months, 12 months, and 30 months.
The results showed a significant reduction in smoking. Patients went from smoking more than 15 cigarettes per day to smoking one to two cigarettes per day before going back up to six cigarettes daily.
Regarding abstinence rates, 12 of 15 patients had stopped smoking after 6 months, 8 of 15 after 1 year, and 7 of 15 after 30 months. “This study produced some interesting results, although caution must obviously be taken due to the very low number of patients enrolled,” said Dr. Roméo.
As is the case for alcohol, a retrospective survey conducted via questionnaire at Paul Brousse Hospital showed that the patients who smoked the most and who had the most mystical psychedelic experiences seemed to respond best to psilocybin and therefore to reduce their tobacco use. It also seemed to be the case that patients who reduced tobacco use the most had lower psychological flexibility on enrollment in the study.
Constraints on psychedelics
“Psychedelics are somewhat effective in treating addiction, but there are various limitations to their use,” said Dr. Roméo.
One of those limitations is societal. Laurence Bézo, MD, of the addiction services clinic at Paul Brousse Hospital, asked doctors to respond to a questionnaire to determine what they thought about psychedelics. To date, 407 have responded, including 280 general practitioners, 50 addiction specialists, and 50 specialist physicians. Overall, 50% think that psychedelics have no therapeutic potential. Three of five doctors also said that psychedelics are dangerous. Just over half thought that their use is associated with a severe risk of aggression aimed at oneself and toward others. Likewise, half think that the risk of dependency is very high and that there is a risk of co-occurring psychiatric disorders. “From the pool of physicians queried, the consensus is that psychedelics are pretty dangerous. People also seem to frown upon prescribing psychedelics in France,” said Dr. Roméo.
Participants went as far as to classify psychedelics as some of the most dangerous drugs out there.
Using a 7-point scale, they classified psychedelics below heroin and cocaine in terms of dangerousness. They are deemed much more harmful than alcohol, tobacco, and cannabis.
“A survey of the public carried out several years ago by leading French market research group IFOP had the exact same findings. Nevertheless, a number of studies have set out to determine how dangerous psychedelics are, and their findings point to this class of drugs as being among the least harmful for the individual patient and those around them. On the contrary, alcohol, heroin, crack cocaine (or even cocaine),methamphetamine, and tobacco were shown to be the most harmful. Additionally, psychedelics have a very low risk of dependency and the lowest risk of lethality. There is complete dissonance between what recent studies show us and what society, and some doctors, think,” said Dr. Roméo.
Besides these assumptions, another constraint to the use of psychedelics relates to methods adopted in related clinical studies. “Due to the effect psychedelics have, in the trials conducted, 9 participants and 9 doctors out of 10 are aware of what they have taken or given, respectively. This is a very important limitation. Nowadays, researchers don’t know how to conduct accurate double-blind studies,” said Dr. Roméo.
In sum, for psychiatrists, psychedelics are promising in addiction therapy, but health care professionals, public authorities, and society as a whole must be better informed about their use, and received ideas must be dispelled.
“The findings need to be replicated, but overall, psychedelics are really quite promising in treating both alcohol and tobacco use disorder. They are generally well tolerated with few serious side effects. There is no deterioration in patients with psychiatric conditions while they are taking psychedelics. And if persistent symptoms of psychosis do occur, which is extremely rare, it’s probably because there are preexisting underlying issues at play. We also don’t see increased blood pressure or any other serious physical anomalies. In a supervised setting, as is the case with studies involving psychotherapeutic support, we can no longer say, in this day and age, that psychedelics are harmful,” said Dr. Roméo.
Dr. Roméo reported no conflicts of interest regarding the content of this article.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
The da Vincian cardiovascular system
FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?
This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.
In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
A visionary view
In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].
In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.
This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.
And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve,
“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”
He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.
A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.
But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.
On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.
“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.
But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.
“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.
But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”
Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”
In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”
Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
Wealth of knowledge
Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.
That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.
The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?
This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.
In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
A visionary view
In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].
In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.
This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.
And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve,
“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”
He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.
A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.
But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.
On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.
“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.
But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.
“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.
But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”
Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”
In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”
Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
Wealth of knowledge
Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.
That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.
The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?
This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.
In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
A visionary view
In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].
In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.
This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.
And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve,
“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”
He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.
A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.
But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.
On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.
“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.
But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.
“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.
But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”
Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”
In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”
Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
Wealth of knowledge
Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.
That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.
The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
WHO advises against nonsugar sweeteners for weight control
These sweeteners include aspartame, acesulfame K, advantame, saccharine, sucralose, stevia, and stevia derivatives.
The recommendation is based on the findings of a systematic review that collected data from 283 studies in adults, children, pregnant women, and mixed populations.
The findings suggest that use of NSSs does not confer any long-term benefit in reducing body fat in adults or children. They also suggest that long-term use of NSSs may have potential undesirable effects.
To clarify, short-term NSS use results in a small reduction in body weight and body mass index in adults without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids, and blood pressure.
Conversely, on a long-term basis, results from prospective cohort studies suggest that higher NSS intake is associated with increased risk for type 2 diabetes, cardiovascular diseases, and all-cause mortality in adults (very low– to low-certainty evidence).
Regarding the risk for cancer, results from case-control studies suggest an association between saccharine intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies.
Relatively fewer studies were found for children, and results were largely inconclusive.
Finally, results for pregnant women suggest that higher NSS intake is associated with increased risk for preterm birth (low-certainty evidence) and possibly adiposity in offspring (very low–certainty evidence).
Reducing sugar consumption
“Replacing free sugars with NSS does not help with weight control in the long-term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” Francesco Branca, MD, PhD, WHO director of the department of nutrition and food safety, said in a press release.
“NSSs are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health,” he added.
Applying the guideline
The recommendation applies to all people except individuals with preexisting diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners, said the WHO.
The recommendation does not apply to personal care and hygiene products containing NSSs, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols).
Because the link observed in the evidence between NSSs and disease outcomes might be confounded by the baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as “conditional” by the WHO.
“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” said the WHO press release.
This article was translated from the Medscape French Edition . A version of the article appeared on Medscape.com.
These sweeteners include aspartame, acesulfame K, advantame, saccharine, sucralose, stevia, and stevia derivatives.
The recommendation is based on the findings of a systematic review that collected data from 283 studies in adults, children, pregnant women, and mixed populations.
The findings suggest that use of NSSs does not confer any long-term benefit in reducing body fat in adults or children. They also suggest that long-term use of NSSs may have potential undesirable effects.
To clarify, short-term NSS use results in a small reduction in body weight and body mass index in adults without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids, and blood pressure.
Conversely, on a long-term basis, results from prospective cohort studies suggest that higher NSS intake is associated with increased risk for type 2 diabetes, cardiovascular diseases, and all-cause mortality in adults (very low– to low-certainty evidence).
Regarding the risk for cancer, results from case-control studies suggest an association between saccharine intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies.
Relatively fewer studies were found for children, and results were largely inconclusive.
Finally, results for pregnant women suggest that higher NSS intake is associated with increased risk for preterm birth (low-certainty evidence) and possibly adiposity in offspring (very low–certainty evidence).
Reducing sugar consumption
“Replacing free sugars with NSS does not help with weight control in the long-term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” Francesco Branca, MD, PhD, WHO director of the department of nutrition and food safety, said in a press release.
“NSSs are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health,” he added.
Applying the guideline
The recommendation applies to all people except individuals with preexisting diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners, said the WHO.
The recommendation does not apply to personal care and hygiene products containing NSSs, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols).
Because the link observed in the evidence between NSSs and disease outcomes might be confounded by the baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as “conditional” by the WHO.
“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” said the WHO press release.
This article was translated from the Medscape French Edition . A version of the article appeared on Medscape.com.
These sweeteners include aspartame, acesulfame K, advantame, saccharine, sucralose, stevia, and stevia derivatives.
The recommendation is based on the findings of a systematic review that collected data from 283 studies in adults, children, pregnant women, and mixed populations.
The findings suggest that use of NSSs does not confer any long-term benefit in reducing body fat in adults or children. They also suggest that long-term use of NSSs may have potential undesirable effects.
To clarify, short-term NSS use results in a small reduction in body weight and body mass index in adults without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids, and blood pressure.
Conversely, on a long-term basis, results from prospective cohort studies suggest that higher NSS intake is associated with increased risk for type 2 diabetes, cardiovascular diseases, and all-cause mortality in adults (very low– to low-certainty evidence).
Regarding the risk for cancer, results from case-control studies suggest an association between saccharine intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies.
Relatively fewer studies were found for children, and results were largely inconclusive.
Finally, results for pregnant women suggest that higher NSS intake is associated with increased risk for preterm birth (low-certainty evidence) and possibly adiposity in offspring (very low–certainty evidence).
Reducing sugar consumption
“Replacing free sugars with NSS does not help with weight control in the long-term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” Francesco Branca, MD, PhD, WHO director of the department of nutrition and food safety, said in a press release.
“NSSs are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health,” he added.
Applying the guideline
The recommendation applies to all people except individuals with preexisting diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners, said the WHO.
The recommendation does not apply to personal care and hygiene products containing NSSs, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols).
Because the link observed in the evidence between NSSs and disease outcomes might be confounded by the baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as “conditional” by the WHO.
“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” said the WHO press release.
This article was translated from the Medscape French Edition . A version of the article appeared on Medscape.com.
Should youth with type 1 diabetes use closed-loop systems?
Would closed-loop systems be a good option for young patients with type 1 diabetes?
International and French recommendations on closed-loop systems state that the use of an “artificial pancreas” should be reserved for adults who are fully engaged with their treatment. This means that young patients, especially adolescents, who are less likely to comply with treatment and are more likely to experience suboptimal blood glucose control, are often excluded from the use of such systems for managing their diabetes.
Several recent studies seem to call this approach into question.
One such study, which was presented at a Francophone Diabetes Society conference and was published in Nature Communications, showed that adolescents with poorly controlled diabetes who were equipped with closed-loop systems gained IQ points and reasoning capacity and experienced a reduction in edematous tissue in the brain cortex. Furthermore, with the closed-loop system, patients spent 13% more time in a target range, and there was a significant reduction in time spent in hyperglycemia.
In the same vein, a small prospective study published in Diabetes Care showed that the closed-loop system with the Minimed 780G pump improved glycemic control for 20 young patients with type 1 diabetes aged 13-25 years whose diabetes was poorly controlled (hemoglobin A1c ≥ 8.5%). At the end of the 3-month study period, the average A1c had decreased from 10.5% (±2.1%) to 7.6% (±1.1%), an average decrease of 2.9%. The time spent in target A1c, which was set from 0.70 g/L to 1.80 g/L, was increased by almost 40%.
With respect to very young children, a study published in The New England Journal of Medicine also showed a favorable risk-benefit ratio for closed-loop systems. The trial, which enrolled 102 children aged 2 years to less than 6 years who had type 1 diabetes, showed that the amount of time that the glucose level was within the target range during the 13-week study period was higher (+3 hours) for those who had been randomly assigned to receive the hybrid closed-loop system (n = 68) than for those who had received the standard treatment (n = 34), either with an insulin pump or multiple daily injections or a Dexcom G6 continuous glucose monitoring device.
A previous study carried out by the Paris Public Hospital System had already shown that the French Diabeloop system could reduce episodes of hypoglycemia and achieve good glycemic control for prepubescent children (n = 21; aged 6-12 years) with type 1 diabetes in real-life conditions.
Eric Renard, MD, PhD, head of the department of endocrinology and diabetes at Lapeyronie Hospital in Montpellier, France, was not surprised at the findings from the study, especially in adolescents with poorly controlled diabetes.
“We have already seen studies in which those patients who had the most poorly controlled diabetes at the start were the ones who improved the most with the closed-loop system, by at least 20% in terms of time in target. These findings resonate with what I see in my clinic,” said Dr. Renard in an interview.
“In my experience, these young adolescents, who neglected their diabetes when they had no devices to help control it, when they had to inject themselves, et cetera ... well, they’re just not the same people when they’re put on a closed-loop system,” he added. “They rise to the challenge, and for the first time, they succeed without making a huge effort, since the algorithm does what they weren’t doing. It’s astonishing to see near-total engagement in these young people when explaining the technology to them and saying, ‘Let’s give it a go.’ These are the very same youngsters who didn’t want to hear about their diabetes in the past. They are delighted and once again involved in managing their condition.”
That’s why Dr. Renard recommends keeping an open mind when considering treatment options for young patients with poorly controlled type 1 diabetes.
“When young people have very poorly controlled diabetes, they risk having cardiovascular complications and damaging their retinas and kidneys,” he said. “If we can get them from 25% to 45% time in target, even if that hasn’t been easy to achieve, this will help save their blood vessels! The only thing we have to be careful of is that we don’t set up a closed-loop system in someone who doesn’t want one. But, if it can manage to spark the interest of a young patient, in most cases, it’s beneficial.”
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Would closed-loop systems be a good option for young patients with type 1 diabetes?
International and French recommendations on closed-loop systems state that the use of an “artificial pancreas” should be reserved for adults who are fully engaged with their treatment. This means that young patients, especially adolescents, who are less likely to comply with treatment and are more likely to experience suboptimal blood glucose control, are often excluded from the use of such systems for managing their diabetes.
Several recent studies seem to call this approach into question.
One such study, which was presented at a Francophone Diabetes Society conference and was published in Nature Communications, showed that adolescents with poorly controlled diabetes who were equipped with closed-loop systems gained IQ points and reasoning capacity and experienced a reduction in edematous tissue in the brain cortex. Furthermore, with the closed-loop system, patients spent 13% more time in a target range, and there was a significant reduction in time spent in hyperglycemia.
In the same vein, a small prospective study published in Diabetes Care showed that the closed-loop system with the Minimed 780G pump improved glycemic control for 20 young patients with type 1 diabetes aged 13-25 years whose diabetes was poorly controlled (hemoglobin A1c ≥ 8.5%). At the end of the 3-month study period, the average A1c had decreased from 10.5% (±2.1%) to 7.6% (±1.1%), an average decrease of 2.9%. The time spent in target A1c, which was set from 0.70 g/L to 1.80 g/L, was increased by almost 40%.
With respect to very young children, a study published in The New England Journal of Medicine also showed a favorable risk-benefit ratio for closed-loop systems. The trial, which enrolled 102 children aged 2 years to less than 6 years who had type 1 diabetes, showed that the amount of time that the glucose level was within the target range during the 13-week study period was higher (+3 hours) for those who had been randomly assigned to receive the hybrid closed-loop system (n = 68) than for those who had received the standard treatment (n = 34), either with an insulin pump or multiple daily injections or a Dexcom G6 continuous glucose monitoring device.
A previous study carried out by the Paris Public Hospital System had already shown that the French Diabeloop system could reduce episodes of hypoglycemia and achieve good glycemic control for prepubescent children (n = 21; aged 6-12 years) with type 1 diabetes in real-life conditions.
Eric Renard, MD, PhD, head of the department of endocrinology and diabetes at Lapeyronie Hospital in Montpellier, France, was not surprised at the findings from the study, especially in adolescents with poorly controlled diabetes.
“We have already seen studies in which those patients who had the most poorly controlled diabetes at the start were the ones who improved the most with the closed-loop system, by at least 20% in terms of time in target. These findings resonate with what I see in my clinic,” said Dr. Renard in an interview.
“In my experience, these young adolescents, who neglected their diabetes when they had no devices to help control it, when they had to inject themselves, et cetera ... well, they’re just not the same people when they’re put on a closed-loop system,” he added. “They rise to the challenge, and for the first time, they succeed without making a huge effort, since the algorithm does what they weren’t doing. It’s astonishing to see near-total engagement in these young people when explaining the technology to them and saying, ‘Let’s give it a go.’ These are the very same youngsters who didn’t want to hear about their diabetes in the past. They are delighted and once again involved in managing their condition.”
That’s why Dr. Renard recommends keeping an open mind when considering treatment options for young patients with poorly controlled type 1 diabetes.
“When young people have very poorly controlled diabetes, they risk having cardiovascular complications and damaging their retinas and kidneys,” he said. “If we can get them from 25% to 45% time in target, even if that hasn’t been easy to achieve, this will help save their blood vessels! The only thing we have to be careful of is that we don’t set up a closed-loop system in someone who doesn’t want one. But, if it can manage to spark the interest of a young patient, in most cases, it’s beneficial.”
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Would closed-loop systems be a good option for young patients with type 1 diabetes?
International and French recommendations on closed-loop systems state that the use of an “artificial pancreas” should be reserved for adults who are fully engaged with their treatment. This means that young patients, especially adolescents, who are less likely to comply with treatment and are more likely to experience suboptimal blood glucose control, are often excluded from the use of such systems for managing their diabetes.
Several recent studies seem to call this approach into question.
One such study, which was presented at a Francophone Diabetes Society conference and was published in Nature Communications, showed that adolescents with poorly controlled diabetes who were equipped with closed-loop systems gained IQ points and reasoning capacity and experienced a reduction in edematous tissue in the brain cortex. Furthermore, with the closed-loop system, patients spent 13% more time in a target range, and there was a significant reduction in time spent in hyperglycemia.
In the same vein, a small prospective study published in Diabetes Care showed that the closed-loop system with the Minimed 780G pump improved glycemic control for 20 young patients with type 1 diabetes aged 13-25 years whose diabetes was poorly controlled (hemoglobin A1c ≥ 8.5%). At the end of the 3-month study period, the average A1c had decreased from 10.5% (±2.1%) to 7.6% (±1.1%), an average decrease of 2.9%. The time spent in target A1c, which was set from 0.70 g/L to 1.80 g/L, was increased by almost 40%.
With respect to very young children, a study published in The New England Journal of Medicine also showed a favorable risk-benefit ratio for closed-loop systems. The trial, which enrolled 102 children aged 2 years to less than 6 years who had type 1 diabetes, showed that the amount of time that the glucose level was within the target range during the 13-week study period was higher (+3 hours) for those who had been randomly assigned to receive the hybrid closed-loop system (n = 68) than for those who had received the standard treatment (n = 34), either with an insulin pump or multiple daily injections or a Dexcom G6 continuous glucose monitoring device.
A previous study carried out by the Paris Public Hospital System had already shown that the French Diabeloop system could reduce episodes of hypoglycemia and achieve good glycemic control for prepubescent children (n = 21; aged 6-12 years) with type 1 diabetes in real-life conditions.
Eric Renard, MD, PhD, head of the department of endocrinology and diabetes at Lapeyronie Hospital in Montpellier, France, was not surprised at the findings from the study, especially in adolescents with poorly controlled diabetes.
“We have already seen studies in which those patients who had the most poorly controlled diabetes at the start were the ones who improved the most with the closed-loop system, by at least 20% in terms of time in target. These findings resonate with what I see in my clinic,” said Dr. Renard in an interview.
“In my experience, these young adolescents, who neglected their diabetes when they had no devices to help control it, when they had to inject themselves, et cetera ... well, they’re just not the same people when they’re put on a closed-loop system,” he added. “They rise to the challenge, and for the first time, they succeed without making a huge effort, since the algorithm does what they weren’t doing. It’s astonishing to see near-total engagement in these young people when explaining the technology to them and saying, ‘Let’s give it a go.’ These are the very same youngsters who didn’t want to hear about their diabetes in the past. They are delighted and once again involved in managing their condition.”
That’s why Dr. Renard recommends keeping an open mind when considering treatment options for young patients with poorly controlled type 1 diabetes.
“When young people have very poorly controlled diabetes, they risk having cardiovascular complications and damaging their retinas and kidneys,” he said. “If we can get them from 25% to 45% time in target, even if that hasn’t been easy to achieve, this will help save their blood vessels! The only thing we have to be careful of is that we don’t set up a closed-loop system in someone who doesn’t want one. But, if it can manage to spark the interest of a young patient, in most cases, it’s beneficial.”
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Exercise or neuromuscular stimulation in type 2 diabetes?
Studies indicate that physical activity improves glucose metabolism in patients with type 2 diabetes. In addition, other data suggest a decrease in cardiovascular morbidity and mortality through physical activity.
In the consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2022,” the American Diabetes Association and the European Association for the Study of Diabetes, therefore, recommend at least 150 minutes per week of moderate- to vigorous-intensity aerobic activity, supplemented with two to three resistance, flexibility, or balance training sessions per week.
But even when such recommendations are integrated into a therapeutic education program, adherence is often transient or partial.
In this context, Michael Joubert, MD, PhD, and his team at Caen (France) University Hospital wondered about neuromuscular electrical stimulation (NMES), a physical treatment routinely used in functional rehabilitation to improve muscle strength and volume.
To answer this question, they conducted a crossover randomized controlled trial called ELECTRODIAB2. The results were presented at the 2023 Congress of the Francophone Diabetes Society.
A few small pilot studies found that NMES improved insulin sensitivity and glycemic control; therefore, it could indeed be an alternative. The metabolic effect of NMES, however, has not been widely studied.
A total of 40 patients were enrolled in ELECTRODIAB2. Of these participants, 35 were randomly assigned to one of three groups: 6 weeks without NMES (control, no intervention), electrostimulation on 3 days per week for 6 weeks (20-minute ambulatory biquadricipital electrostimulation sessions) (NMES3), and electrostimulation on 5 days per week for 6 weeks (20-minutes ambulatory biquadricipital electrostimulation sessions) (NMES5). The goal was to assess the glucose levels of sedentary patients with type 2 diabetes during these periods. At each session, NMES was applied at the maximum-tolerated intensity.
Data from 32 participants were analyzed. Mean age was 58 ± 10 years, and body mass index was 33.0 ± 4.3 kg/m2. Duration of diabetes was 8.6 ± 5.9 years. Regarding diabetes treatments, 47%, 31%, 9%, and 13% of the patients were taking 0, 1, 2, and 3 oral hypoglycemic agents or glucagonlike peptide–1 agonists, respectively.
No significant differences in glucose levels were observed between the three groups. The primary outcome was mean glucose level based on a 6-day continuous glucose monitoring (CGM) recording. Those levels were 181.4 ± 42.5 mg/dL (control, no intervention), 180.6 ± 45.8 mg/dL (NMES3), and 181.1 ± 48.9 mg/dL (NMES5).
Furthermore, secondary outcomes (rates of hyperglycemia and hypoglycemia) did not differ between the three groups.
The researchers concluded that, “with regard to the CGM criteria, this crossover randomized controlled trial did not show that the 6-week biquadricipital NMES sessions had any benefit. This finding conflicts with the results of preliminary pilot studies but it does not encourage further research on NMES in this population of patients with early-stage diabetes.”
Therefore, at this point, it does not look like NMES can be recommended as an alternative to physical activity for sedentary patients with type 2 diabetes.
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Studies indicate that physical activity improves glucose metabolism in patients with type 2 diabetes. In addition, other data suggest a decrease in cardiovascular morbidity and mortality through physical activity.
In the consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2022,” the American Diabetes Association and the European Association for the Study of Diabetes, therefore, recommend at least 150 minutes per week of moderate- to vigorous-intensity aerobic activity, supplemented with two to three resistance, flexibility, or balance training sessions per week.
But even when such recommendations are integrated into a therapeutic education program, adherence is often transient or partial.
In this context, Michael Joubert, MD, PhD, and his team at Caen (France) University Hospital wondered about neuromuscular electrical stimulation (NMES), a physical treatment routinely used in functional rehabilitation to improve muscle strength and volume.
To answer this question, they conducted a crossover randomized controlled trial called ELECTRODIAB2. The results were presented at the 2023 Congress of the Francophone Diabetes Society.
A few small pilot studies found that NMES improved insulin sensitivity and glycemic control; therefore, it could indeed be an alternative. The metabolic effect of NMES, however, has not been widely studied.
A total of 40 patients were enrolled in ELECTRODIAB2. Of these participants, 35 were randomly assigned to one of three groups: 6 weeks without NMES (control, no intervention), electrostimulation on 3 days per week for 6 weeks (20-minute ambulatory biquadricipital electrostimulation sessions) (NMES3), and electrostimulation on 5 days per week for 6 weeks (20-minutes ambulatory biquadricipital electrostimulation sessions) (NMES5). The goal was to assess the glucose levels of sedentary patients with type 2 diabetes during these periods. At each session, NMES was applied at the maximum-tolerated intensity.
Data from 32 participants were analyzed. Mean age was 58 ± 10 years, and body mass index was 33.0 ± 4.3 kg/m2. Duration of diabetes was 8.6 ± 5.9 years. Regarding diabetes treatments, 47%, 31%, 9%, and 13% of the patients were taking 0, 1, 2, and 3 oral hypoglycemic agents or glucagonlike peptide–1 agonists, respectively.
No significant differences in glucose levels were observed between the three groups. The primary outcome was mean glucose level based on a 6-day continuous glucose monitoring (CGM) recording. Those levels were 181.4 ± 42.5 mg/dL (control, no intervention), 180.6 ± 45.8 mg/dL (NMES3), and 181.1 ± 48.9 mg/dL (NMES5).
Furthermore, secondary outcomes (rates of hyperglycemia and hypoglycemia) did not differ between the three groups.
The researchers concluded that, “with regard to the CGM criteria, this crossover randomized controlled trial did not show that the 6-week biquadricipital NMES sessions had any benefit. This finding conflicts with the results of preliminary pilot studies but it does not encourage further research on NMES in this population of patients with early-stage diabetes.”
Therefore, at this point, it does not look like NMES can be recommended as an alternative to physical activity for sedentary patients with type 2 diabetes.
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Studies indicate that physical activity improves glucose metabolism in patients with type 2 diabetes. In addition, other data suggest a decrease in cardiovascular morbidity and mortality through physical activity.
In the consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2022,” the American Diabetes Association and the European Association for the Study of Diabetes, therefore, recommend at least 150 minutes per week of moderate- to vigorous-intensity aerobic activity, supplemented with two to three resistance, flexibility, or balance training sessions per week.
But even when such recommendations are integrated into a therapeutic education program, adherence is often transient or partial.
In this context, Michael Joubert, MD, PhD, and his team at Caen (France) University Hospital wondered about neuromuscular electrical stimulation (NMES), a physical treatment routinely used in functional rehabilitation to improve muscle strength and volume.
To answer this question, they conducted a crossover randomized controlled trial called ELECTRODIAB2. The results were presented at the 2023 Congress of the Francophone Diabetes Society.
A few small pilot studies found that NMES improved insulin sensitivity and glycemic control; therefore, it could indeed be an alternative. The metabolic effect of NMES, however, has not been widely studied.
A total of 40 patients were enrolled in ELECTRODIAB2. Of these participants, 35 were randomly assigned to one of three groups: 6 weeks without NMES (control, no intervention), electrostimulation on 3 days per week for 6 weeks (20-minute ambulatory biquadricipital electrostimulation sessions) (NMES3), and electrostimulation on 5 days per week for 6 weeks (20-minutes ambulatory biquadricipital electrostimulation sessions) (NMES5). The goal was to assess the glucose levels of sedentary patients with type 2 diabetes during these periods. At each session, NMES was applied at the maximum-tolerated intensity.
Data from 32 participants were analyzed. Mean age was 58 ± 10 years, and body mass index was 33.0 ± 4.3 kg/m2. Duration of diabetes was 8.6 ± 5.9 years. Regarding diabetes treatments, 47%, 31%, 9%, and 13% of the patients were taking 0, 1, 2, and 3 oral hypoglycemic agents or glucagonlike peptide–1 agonists, respectively.
No significant differences in glucose levels were observed between the three groups. The primary outcome was mean glucose level based on a 6-day continuous glucose monitoring (CGM) recording. Those levels were 181.4 ± 42.5 mg/dL (control, no intervention), 180.6 ± 45.8 mg/dL (NMES3), and 181.1 ± 48.9 mg/dL (NMES5).
Furthermore, secondary outcomes (rates of hyperglycemia and hypoglycemia) did not differ between the three groups.
The researchers concluded that, “with regard to the CGM criteria, this crossover randomized controlled trial did not show that the 6-week biquadricipital NMES sessions had any benefit. This finding conflicts with the results of preliminary pilot studies but it does not encourage further research on NMES in this population of patients with early-stage diabetes.”
Therefore, at this point, it does not look like NMES can be recommended as an alternative to physical activity for sedentary patients with type 2 diabetes.
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Can siRNA improve compliance in patients with hypertension?
Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.
It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.
These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.
The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.
This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
Lasting efficacy
Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.
“It’s extremely powerful,” said Dr. Azizi.
Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).
Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.
“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
Unanswered questions
The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.
In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.
Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.
However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.
A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.
Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.
In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
On the horizon
Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).
This article was translated from the Medscape French edition and a version appeared on Medscape.com.
Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.
It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.
These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.
The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.
This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
Lasting efficacy
Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.
“It’s extremely powerful,” said Dr. Azizi.
Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).
Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.
“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
Unanswered questions
The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.
In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.
Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.
However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.
A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.
Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.
In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
On the horizon
Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).
This article was translated from the Medscape French edition and a version appeared on Medscape.com.
Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.
It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.
These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.
The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.
This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
Lasting efficacy
Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.
“It’s extremely powerful,” said Dr. Azizi.
Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).
Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.
“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
Unanswered questions
The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.
In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.
Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.
However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.
A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.
Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.
In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
On the horizon
Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).
This article was translated from the Medscape French edition and a version appeared on Medscape.com.
AT INTERNATIONAL MEETING OF THE FRENCH SOCIETY OF HYPERTENSION
Is a single dose of HPV vaccine enough?
In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.
This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides protection against persistent infection from HPV 16 and 18 similar to that provided by two or three doses.
Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.
With respect to the Indian study, Dr. Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless,
India and France
During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.
“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.
“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Dr. Canlorbe.
“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.
This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.
In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
Indian study highlights
Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.
According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Dr. Basu and his team had recruited 17,729 eligible girls.
After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.
Vaccinated participants were followed up over a median duration of 9 years. In all, 4,348 participants had three doses, 4,980 had two doses (at 0 and 6 months), and 4,949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.
A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% confidence interval [CI], 85.0-99.9) in the single-dose default cohort (2,135 women assessed), 93.1% (95% CI, 77.3-99.8) in the two-dose cohort (1,452 women assessed), and 93.3% (95% CI, 77.5-99.7) in three-dose recipients (1,460 women assessed).
Dr. Canlorbe reported no relevant financial relationships regarding the content of this article.
This article was translated from the Medscape French edition. An English version appeared on Medscape.com.
In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.
This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides protection against persistent infection from HPV 16 and 18 similar to that provided by two or three doses.
Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.
With respect to the Indian study, Dr. Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless,
India and France
During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.
“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.
“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Dr. Canlorbe.
“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.
This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.
In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
Indian study highlights
Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.
According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Dr. Basu and his team had recruited 17,729 eligible girls.
After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.
Vaccinated participants were followed up over a median duration of 9 years. In all, 4,348 participants had three doses, 4,980 had two doses (at 0 and 6 months), and 4,949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.
A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% confidence interval [CI], 85.0-99.9) in the single-dose default cohort (2,135 women assessed), 93.1% (95% CI, 77.3-99.8) in the two-dose cohort (1,452 women assessed), and 93.3% (95% CI, 77.5-99.7) in three-dose recipients (1,460 women assessed).
Dr. Canlorbe reported no relevant financial relationships regarding the content of this article.
This article was translated from the Medscape French edition. An English version appeared on Medscape.com.
In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.
This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides protection against persistent infection from HPV 16 and 18 similar to that provided by two or three doses.
Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.
With respect to the Indian study, Dr. Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless,
India and France
During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.
“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.
“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Dr. Canlorbe.
“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.
This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.
In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
Indian study highlights
Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.
According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Dr. Basu and his team had recruited 17,729 eligible girls.
After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.
Vaccinated participants were followed up over a median duration of 9 years. In all, 4,348 participants had three doses, 4,980 had two doses (at 0 and 6 months), and 4,949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.
A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% confidence interval [CI], 85.0-99.9) in the single-dose default cohort (2,135 women assessed), 93.1% (95% CI, 77.3-99.8) in the two-dose cohort (1,452 women assessed), and 93.3% (95% CI, 77.5-99.7) in three-dose recipients (1,460 women assessed).
Dr. Canlorbe reported no relevant financial relationships regarding the content of this article.
This article was translated from the Medscape French edition. An English version appeared on Medscape.com.