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FMT Could Prevent Recurrence of Hepatic Encephalopathy in Patients With Cirrhosis
MILAN — , results of a phase 2 randomized controlled trial show.
“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.
Donor background (including vegan or omnivore) and dose range also did not affect the efficacy of FMT, Dr. Bajaj said.
Dr. Bajaj presented the findings (Abstract GS-001) at the opening session of the annual European Association for the Study of the Liver (EASL) Congress 2024.
Hepatic encephalopathy is a complication of advanced liver disease that causes a dementia-like state. Standard treatment with lactulose and rifaximin often results in a lack of patient response, meaning the patient is constantly being readmitted to the hospital, Dr. Bajaj said.
“This is a burden for the family as well as the patients,” and is very difficult to manage from a clinical and psychosocial perspective, he said in an interview.
With FMT, “we are transferring an ecosystem of good microbes,” which modifies the gut microbiome in patients with advanced liver disease and reduces associated brain toxicity, Dr. Bajaj explained.
Resetting the Gut
The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior.
Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded.
Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4).
The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart.
Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care.
“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”
Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
One Dose of FMT Better Than None
Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%).
SIP total/physical and psych scores improved with FMT (P = .003).
When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence.
Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups.
“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.
Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT.
“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”
He pointed out that in smaller prior studies, the effects lasted up to 1 year.
Setting the Stage for Phase 3 Trials
Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy.
“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.
This study was built on Dr. Bajaj’s prior work that established the safety of FMT by enema, she added, stressing that this new research was incredibly important in these immunocompromised patients who are at higher risk for infection transmission.
That the administration route doesn’t matter is also an important finding as oral administration is much more feasible than enema, said Dr. Kelly, who went on to point out the importance of finding an alternative to rifaximin and lactulose, which are often poorly tolerated.
The study highlights the central role played by the gut microbiota in dysbiosis in the pathophysiology of hepatic encephalopathy, Dr. Kelly said. “It is another exciting example of how gut microbiota can be manipulated to treat disease.”
Dr. Bajaj and Dr. Kelly report no relevant financial relationships to this study.
A version of this article appeared on Medscape.com.
MILAN — , results of a phase 2 randomized controlled trial show.
“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.
Donor background (including vegan or omnivore) and dose range also did not affect the efficacy of FMT, Dr. Bajaj said.
Dr. Bajaj presented the findings (Abstract GS-001) at the opening session of the annual European Association for the Study of the Liver (EASL) Congress 2024.
Hepatic encephalopathy is a complication of advanced liver disease that causes a dementia-like state. Standard treatment with lactulose and rifaximin often results in a lack of patient response, meaning the patient is constantly being readmitted to the hospital, Dr. Bajaj said.
“This is a burden for the family as well as the patients,” and is very difficult to manage from a clinical and psychosocial perspective, he said in an interview.
With FMT, “we are transferring an ecosystem of good microbes,” which modifies the gut microbiome in patients with advanced liver disease and reduces associated brain toxicity, Dr. Bajaj explained.
Resetting the Gut
The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior.
Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded.
Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4).
The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart.
Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care.
“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”
Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
One Dose of FMT Better Than None
Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%).
SIP total/physical and psych scores improved with FMT (P = .003).
When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence.
Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups.
“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.
Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT.
“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”
He pointed out that in smaller prior studies, the effects lasted up to 1 year.
Setting the Stage for Phase 3 Trials
Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy.
“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.
This study was built on Dr. Bajaj’s prior work that established the safety of FMT by enema, she added, stressing that this new research was incredibly important in these immunocompromised patients who are at higher risk for infection transmission.
That the administration route doesn’t matter is also an important finding as oral administration is much more feasible than enema, said Dr. Kelly, who went on to point out the importance of finding an alternative to rifaximin and lactulose, which are often poorly tolerated.
The study highlights the central role played by the gut microbiota in dysbiosis in the pathophysiology of hepatic encephalopathy, Dr. Kelly said. “It is another exciting example of how gut microbiota can be manipulated to treat disease.”
Dr. Bajaj and Dr. Kelly report no relevant financial relationships to this study.
A version of this article appeared on Medscape.com.
MILAN — , results of a phase 2 randomized controlled trial show.
“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.
Donor background (including vegan or omnivore) and dose range also did not affect the efficacy of FMT, Dr. Bajaj said.
Dr. Bajaj presented the findings (Abstract GS-001) at the opening session of the annual European Association for the Study of the Liver (EASL) Congress 2024.
Hepatic encephalopathy is a complication of advanced liver disease that causes a dementia-like state. Standard treatment with lactulose and rifaximin often results in a lack of patient response, meaning the patient is constantly being readmitted to the hospital, Dr. Bajaj said.
“This is a burden for the family as well as the patients,” and is very difficult to manage from a clinical and psychosocial perspective, he said in an interview.
With FMT, “we are transferring an ecosystem of good microbes,” which modifies the gut microbiome in patients with advanced liver disease and reduces associated brain toxicity, Dr. Bajaj explained.
Resetting the Gut
The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior.
Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded.
Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4).
The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart.
Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care.
“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”
Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
One Dose of FMT Better Than None
Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%).
SIP total/physical and psych scores improved with FMT (P = .003).
When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence.
Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups.
“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.
Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT.
“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”
He pointed out that in smaller prior studies, the effects lasted up to 1 year.
Setting the Stage for Phase 3 Trials
Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy.
“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.
This study was built on Dr. Bajaj’s prior work that established the safety of FMT by enema, she added, stressing that this new research was incredibly important in these immunocompromised patients who are at higher risk for infection transmission.
That the administration route doesn’t matter is also an important finding as oral administration is much more feasible than enema, said Dr. Kelly, who went on to point out the importance of finding an alternative to rifaximin and lactulose, which are often poorly tolerated.
The study highlights the central role played by the gut microbiota in dysbiosis in the pathophysiology of hepatic encephalopathy, Dr. Kelly said. “It is another exciting example of how gut microbiota can be manipulated to treat disease.”
Dr. Bajaj and Dr. Kelly report no relevant financial relationships to this study.
A version of this article appeared on Medscape.com.
FROM EASL 2024
Seniors in Households with Children Have Sixfold Higher Risk for Pneumococcal Disease
BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.
However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”
The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.
Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.
The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
Originally Designed to Investigate Adult-to-Adult Transmission
The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.
Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”
Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.
The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.
Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
Strongly Suggestive of Transmission From Children to Older Adults
Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.
Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.
There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.
Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.
At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).
In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.
The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.
Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.
“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.
However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.
This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”
“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.
Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
A version of this article appeared on Medscape.com.
BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.
However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”
The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.
Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.
The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
Originally Designed to Investigate Adult-to-Adult Transmission
The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.
Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”
Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.
The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.
Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
Strongly Suggestive of Transmission From Children to Older Adults
Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.
Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.
There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.
Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.
At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).
In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.
The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.
Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.
“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.
However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.
This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”
“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.
Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
A version of this article appeared on Medscape.com.
BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.
However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”
The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.
Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.
The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
Originally Designed to Investigate Adult-to-Adult Transmission
The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.
Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”
Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.
The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.
Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
Strongly Suggestive of Transmission From Children to Older Adults
Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.
Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.
There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.
Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.
At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).
In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.
The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.
Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.
“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.
However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.
This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”
“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.
Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
A version of this article appeared on Medscape.com.
FROM ESCMID GLOBAL 2024
Is Body Fat a Better Measure of Obesity in Midlife Than BMI?
VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.
Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians.
Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.
“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.
BMI Limitations Misses Body Composition
If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.
[for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out.
This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups.
The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.
The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity.
Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30.
The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences.
Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases
In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher.
“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.”
Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.
“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”
Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene.
Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?
“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded.
Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience.
A version of this article appeared on Medscape.com.
VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.
Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians.
Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.
“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.
BMI Limitations Misses Body Composition
If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.
[for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out.
This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups.
The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.
The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity.
Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30.
The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences.
Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases
In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher.
“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.”
Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.
“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”
Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene.
Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?
“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded.
Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience.
A version of this article appeared on Medscape.com.
VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.
Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians.
Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.
“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.
BMI Limitations Misses Body Composition
If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.
[for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out.
This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups.
The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.
The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity.
Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30.
The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences.
Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases
In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher.
“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.”
Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.
“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”
Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene.
Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?
“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded.
Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience.
A version of this article appeared on Medscape.com.
Temporary Gut Liner Lowers Weight, A1c
LONDON — , showed data.
Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.
Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.
“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.
Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
Convenient, Reversible Procedure
Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.
Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.
The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.
“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.
Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
Over Half Maintained Full Improvement 2 Years Post Removal
A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m2, and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.
Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.
Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m2, A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.
Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).
Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.
Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.
Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.
Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”
Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.
EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m2.
A version of this article appeared on Medscape.com.
LONDON — , showed data.
Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.
Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.
“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.
Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
Convenient, Reversible Procedure
Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.
Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.
The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.
“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.
Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
Over Half Maintained Full Improvement 2 Years Post Removal
A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m2, and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.
Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.
Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m2, A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.
Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).
Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.
Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.
Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.
Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”
Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.
EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m2.
A version of this article appeared on Medscape.com.
LONDON — , showed data.
Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.
Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.
“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.
Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
Convenient, Reversible Procedure
Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.
Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.
The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.
“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.
Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
Over Half Maintained Full Improvement 2 Years Post Removal
A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m2, and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.
Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.
Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m2, A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.
Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).
Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.
Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.
Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.
Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”
Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.
EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m2.
A version of this article appeared on Medscape.com.
AI Identifies Two Natural Bioactive GLP-1 Compounds
Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.
Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).
Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.
Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.
In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.
“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.
“These are synthetic, and we were interested in finding natural alternatives,” she added.
Natural Versions of Compounds That Activate GLP-1Rs
Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.
Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.
“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.
Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”
“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”
Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.
Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).
Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.
Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.
In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.
“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.
“These are synthetic, and we were interested in finding natural alternatives,” she added.
Natural Versions of Compounds That Activate GLP-1Rs
Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.
Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.
“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.
Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”
“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”
Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.
Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).
Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.
Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.
In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.
“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.
“These are synthetic, and we were interested in finding natural alternatives,” she added.
Natural Versions of Compounds That Activate GLP-1Rs
Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.
Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.
“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.
Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”
“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”
Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.
A version of this article appeared on Medscape.com.
Tirzepatide Weight Loss Consistent Regardless of BMI
Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
Body Weight and Waist Circumference Reduced Regardless of Disease Duration
In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.
Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.
For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.
Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.
A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.
Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.
“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”
“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.
This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”
Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”
Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.
He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”
Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.
Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.
A version of this article appeared on Medscape.com.
Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
Body Weight and Waist Circumference Reduced Regardless of Disease Duration
In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.
Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.
For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.
Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.
A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.
Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.
“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”
“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.
This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”
Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”
Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.
He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”
Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.
Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.
A version of this article appeared on Medscape.com.
Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
Body Weight and Waist Circumference Reduced Regardless of Disease Duration
In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.
Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.
For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.
Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.
A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.
Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.
“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”
“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.
This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”
Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”
Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.
He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”
Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.
Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.
A version of this article appeared on Medscape.com.
AI-Identified Vascular Healing Can Predict Clinical Relapse in Ulcerative Colitis
STOCKHOLM — , according to data from the study of a novel investigational tool.
Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.
In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said.
Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said.
“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.”
Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.
Stratifying the Relapse Risk
Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC.
The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes.
“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.
In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1).
Patient characteristics were similar between both groups with an average disease duration of 10 years.
In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.
In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.
Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.
The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI.
“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.
They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience.
Still in the Early Stages
AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria.
We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said.
The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.
Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to data from the study of a novel investigational tool.
Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.
In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said.
Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said.
“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.”
Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.
Stratifying the Relapse Risk
Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC.
The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes.
“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.
In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1).
Patient characteristics were similar between both groups with an average disease duration of 10 years.
In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.
In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.
Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.
The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI.
“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.
They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience.
Still in the Early Stages
AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria.
We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said.
The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.
Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to data from the study of a novel investigational tool.
Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.
In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said.
Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said.
“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.”
Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.
Stratifying the Relapse Risk
Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC.
The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes.
“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.
In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1).
Patient characteristics were similar between both groups with an average disease duration of 10 years.
In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.
In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.
Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.
The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI.
“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.
They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience.
Still in the Early Stages
AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria.
We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said.
The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.
Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.
A version of this article appeared on Medscape.com.
FROM ECCO 2024
Novel Biotherapeutic to Be Tested in Ulcerative Colitis
STOCKHOLM —
The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.
In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product.
In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.
On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).
Calming Inflammation With Specific Bacteria
To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.
The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.
“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”
Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response.
“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.
Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule.
The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions.
The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation.
The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages.
And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.
Moving in the Right Direction
Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.
“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.
“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.
“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.
Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.
A version of this article appeared on Medscape.com.
STOCKHOLM —
The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.
In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product.
In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.
On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).
Calming Inflammation With Specific Bacteria
To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.
The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.
“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”
Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response.
“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.
Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule.
The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions.
The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation.
The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages.
And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.
Moving in the Right Direction
Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.
“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.
“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.
“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.
Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.
A version of this article appeared on Medscape.com.
STOCKHOLM —
The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.
In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product.
In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.
On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).
Calming Inflammation With Specific Bacteria
To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.
The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.
“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”
Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response.
“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.
Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule.
The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions.
The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation.
The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages.
And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.
Moving in the Right Direction
Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.
“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.
“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.
“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.
Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.
A version of this article appeared on Medscape.com.
FROM ECCO 2024
Is Adrenal Fatigue a Real Condition?
While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”
Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.
“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.
Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress.
Adrenal Fatigue, Burnout, or Adrenal Insufficiency?
Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”
Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.
More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.
He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.
“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.
The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.
“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.
Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.
“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said.
This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.
While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.
“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.
Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.
“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”
Recognizing and Managing Patient Frustration
The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.
Dr. Rao empathizes with the situation that many people, often young women, find themselves in.
“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”
This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.
But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.
“We truly are what we eat, and we are what we think,” she noted.
The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.”
“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”
Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.
“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”
Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.
A version of this article appeared on Medscape.com.
While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”
Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.
“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.
Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress.
Adrenal Fatigue, Burnout, or Adrenal Insufficiency?
Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”
Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.
More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.
He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.
“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.
The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.
“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.
Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.
“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said.
This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.
While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.
“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.
Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.
“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”
Recognizing and Managing Patient Frustration
The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.
Dr. Rao empathizes with the situation that many people, often young women, find themselves in.
“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”
This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.
But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.
“We truly are what we eat, and we are what we think,” she noted.
The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.”
“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”
Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.
“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”
Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.
A version of this article appeared on Medscape.com.
While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”
Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.
“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.
Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress.
Adrenal Fatigue, Burnout, or Adrenal Insufficiency?
Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”
Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.
More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.
He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.
“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.
The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.
“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.
Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.
“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said.
This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.
While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.
“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.
Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.
“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”
Recognizing and Managing Patient Frustration
The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.
Dr. Rao empathizes with the situation that many people, often young women, find themselves in.
“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”
This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.
But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.
“We truly are what we eat, and we are what we think,” she noted.
The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.”
“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”
Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.
“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”
Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.
A version of this article appeared on Medscape.com.
Risankizumab in Crohn’s Disease: Clinical, Endoscopic Outcomes Remain Stable for up to 3 Years
STOCKHOLM — , according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”
Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”
Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents.
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”
Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents.
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
A version of this article appeared on Medscape.com.
FROM ECCO 2024