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People of color missing in inflammatory bowel disease trials
LAS VEGAS – Clinical trials of treatments for inflammatory bowel disease (IBD) have disproportionately enrolled White people, researchers say.
These skewed demographics could result in researchers overlooking differences in how the disease and its treatments might affect other racial and ethnic groups, said Jellyana Peraza, MD, a chief resident at Albert Einstein College of Medicine, New York.
“The only way we can determine that therapies work differently in different populations is by including those populations in these clinical trials,” she said in an interview. “We think that diversity should be present, and that will answer some questions about the pathogenesis of the disease in general.”
Dr. Peraza presented the findings at the annual meeting of the American College of Gastroenterology.
Previous studies have found that, in trials of other conditions, such as cancer and cardiovascular disease, White people have been disproportionately represented. However, little research has been conducted regarding race and ethnicity in IBD trials.
To fill that gap, Dr. Peraza and colleagues analyzed data from completed trials through the U.S. National Library of Medicine’s registry, ClinicalTrials.gov, for the period from 2000 to 2020.
They found 22 trials conducted exclusively in the United States and 56 conducted in other countries that reported the race or ethnicity of participants; 54 trials did not include this information.
With regard to the prevalence of IBD in White people and Asian people, these populations were overrepresented in U.S. clinical trials. All other groups were underrepresented.
The researchers calculated the odds ratio of being included in an IBD clinical trial for each group. Compared with White people, all the other groups were less likely to be included except for Asian people, who were 85% more likely to be included. These ORs were all statistically significant (P < .03) except for Hispanic people (OR, 0.81; 95% confidence interval, 0.65-1.01; P = .06).
It’s not clear why Asian people are overrepresented, Dr. Peraza said. “Honestly, that was kind of surprising for us. We initially thought that could be related to where these studies were conducted, for example, if some of them were conducted on the West Coast, where maybe more Asian communities are located. However, we didn’t find any specific association between location and Asian representation.”
IBD is more prevalent among White people, although its prevalence is increasing among other groups, Dr. Peraza said. However, that is not reflected in the trials. In an analysis of data in 5-year increments, the researchers found that the participation of White and Hispanic people in IBD trials had not changed much, whereas the participation of Black people had declined, and the participation of Asian and Native American people had increased.
On the basis of work of other researchers, Dr. Peraza said that people of color are as willing to participate in trials as White people. “There is not so much a mistrust as a lack of education and a lack of access to the tertiary centers or the centers where these studies are conducted,” she said.
Clinical trial investigators should recruit more participants from community centers, and health care practitioners should talk about the trials with people in underrepresented groups, she said. “They should have the conversation with their patients about how these clinical trials can benefit the evolution of their diseases.”
One research center that is working hard to diversify its IBD trials is the Ohio State University IBD Center, Columbus, said Anita Afzali, MD, its medical director.
“We have a great team that works actively on the recruitment of all patients,” she said in an interview. “Oftentimes, it just takes a little bit of education and spending time with the patient on discussing what the options are for them.”
Some research indicates that Black people with IBD are more likely to have fistulizing disease, Dr. Afzali said. “However, it doesn’t come so much of their differences in phenotype that we’re seeing but more so the differences in access to care and getting the appropriate therapy in a timely way.”
Dr. Peraza and Dr. Afzali disclosed no relevant financial relationships.
AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.
A version of this article first appeared on Medscape.com.
LAS VEGAS – Clinical trials of treatments for inflammatory bowel disease (IBD) have disproportionately enrolled White people, researchers say.
These skewed demographics could result in researchers overlooking differences in how the disease and its treatments might affect other racial and ethnic groups, said Jellyana Peraza, MD, a chief resident at Albert Einstein College of Medicine, New York.
“The only way we can determine that therapies work differently in different populations is by including those populations in these clinical trials,” she said in an interview. “We think that diversity should be present, and that will answer some questions about the pathogenesis of the disease in general.”
Dr. Peraza presented the findings at the annual meeting of the American College of Gastroenterology.
Previous studies have found that, in trials of other conditions, such as cancer and cardiovascular disease, White people have been disproportionately represented. However, little research has been conducted regarding race and ethnicity in IBD trials.
To fill that gap, Dr. Peraza and colleagues analyzed data from completed trials through the U.S. National Library of Medicine’s registry, ClinicalTrials.gov, for the period from 2000 to 2020.
They found 22 trials conducted exclusively in the United States and 56 conducted in other countries that reported the race or ethnicity of participants; 54 trials did not include this information.
With regard to the prevalence of IBD in White people and Asian people, these populations were overrepresented in U.S. clinical trials. All other groups were underrepresented.
The researchers calculated the odds ratio of being included in an IBD clinical trial for each group. Compared with White people, all the other groups were less likely to be included except for Asian people, who were 85% more likely to be included. These ORs were all statistically significant (P < .03) except for Hispanic people (OR, 0.81; 95% confidence interval, 0.65-1.01; P = .06).
It’s not clear why Asian people are overrepresented, Dr. Peraza said. “Honestly, that was kind of surprising for us. We initially thought that could be related to where these studies were conducted, for example, if some of them were conducted on the West Coast, where maybe more Asian communities are located. However, we didn’t find any specific association between location and Asian representation.”
IBD is more prevalent among White people, although its prevalence is increasing among other groups, Dr. Peraza said. However, that is not reflected in the trials. In an analysis of data in 5-year increments, the researchers found that the participation of White and Hispanic people in IBD trials had not changed much, whereas the participation of Black people had declined, and the participation of Asian and Native American people had increased.
On the basis of work of other researchers, Dr. Peraza said that people of color are as willing to participate in trials as White people. “There is not so much a mistrust as a lack of education and a lack of access to the tertiary centers or the centers where these studies are conducted,” she said.
Clinical trial investigators should recruit more participants from community centers, and health care practitioners should talk about the trials with people in underrepresented groups, she said. “They should have the conversation with their patients about how these clinical trials can benefit the evolution of their diseases.”
One research center that is working hard to diversify its IBD trials is the Ohio State University IBD Center, Columbus, said Anita Afzali, MD, its medical director.
“We have a great team that works actively on the recruitment of all patients,” she said in an interview. “Oftentimes, it just takes a little bit of education and spending time with the patient on discussing what the options are for them.”
Some research indicates that Black people with IBD are more likely to have fistulizing disease, Dr. Afzali said. “However, it doesn’t come so much of their differences in phenotype that we’re seeing but more so the differences in access to care and getting the appropriate therapy in a timely way.”
Dr. Peraza and Dr. Afzali disclosed no relevant financial relationships.
AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.
A version of this article first appeared on Medscape.com.
LAS VEGAS – Clinical trials of treatments for inflammatory bowel disease (IBD) have disproportionately enrolled White people, researchers say.
These skewed demographics could result in researchers overlooking differences in how the disease and its treatments might affect other racial and ethnic groups, said Jellyana Peraza, MD, a chief resident at Albert Einstein College of Medicine, New York.
“The only way we can determine that therapies work differently in different populations is by including those populations in these clinical trials,” she said in an interview. “We think that diversity should be present, and that will answer some questions about the pathogenesis of the disease in general.”
Dr. Peraza presented the findings at the annual meeting of the American College of Gastroenterology.
Previous studies have found that, in trials of other conditions, such as cancer and cardiovascular disease, White people have been disproportionately represented. However, little research has been conducted regarding race and ethnicity in IBD trials.
To fill that gap, Dr. Peraza and colleagues analyzed data from completed trials through the U.S. National Library of Medicine’s registry, ClinicalTrials.gov, for the period from 2000 to 2020.
They found 22 trials conducted exclusively in the United States and 56 conducted in other countries that reported the race or ethnicity of participants; 54 trials did not include this information.
With regard to the prevalence of IBD in White people and Asian people, these populations were overrepresented in U.S. clinical trials. All other groups were underrepresented.
The researchers calculated the odds ratio of being included in an IBD clinical trial for each group. Compared with White people, all the other groups were less likely to be included except for Asian people, who were 85% more likely to be included. These ORs were all statistically significant (P < .03) except for Hispanic people (OR, 0.81; 95% confidence interval, 0.65-1.01; P = .06).
It’s not clear why Asian people are overrepresented, Dr. Peraza said. “Honestly, that was kind of surprising for us. We initially thought that could be related to where these studies were conducted, for example, if some of them were conducted on the West Coast, where maybe more Asian communities are located. However, we didn’t find any specific association between location and Asian representation.”
IBD is more prevalent among White people, although its prevalence is increasing among other groups, Dr. Peraza said. However, that is not reflected in the trials. In an analysis of data in 5-year increments, the researchers found that the participation of White and Hispanic people in IBD trials had not changed much, whereas the participation of Black people had declined, and the participation of Asian and Native American people had increased.
On the basis of work of other researchers, Dr. Peraza said that people of color are as willing to participate in trials as White people. “There is not so much a mistrust as a lack of education and a lack of access to the tertiary centers or the centers where these studies are conducted,” she said.
Clinical trial investigators should recruit more participants from community centers, and health care practitioners should talk about the trials with people in underrepresented groups, she said. “They should have the conversation with their patients about how these clinical trials can benefit the evolution of their diseases.”
One research center that is working hard to diversify its IBD trials is the Ohio State University IBD Center, Columbus, said Anita Afzali, MD, its medical director.
“We have a great team that works actively on the recruitment of all patients,” she said in an interview. “Oftentimes, it just takes a little bit of education and spending time with the patient on discussing what the options are for them.”
Some research indicates that Black people with IBD are more likely to have fistulizing disease, Dr. Afzali said. “However, it doesn’t come so much of their differences in phenotype that we’re seeing but more so the differences in access to care and getting the appropriate therapy in a timely way.”
Dr. Peraza and Dr. Afzali disclosed no relevant financial relationships.
AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.
A version of this article first appeared on Medscape.com.
AT ACG 2021
Endoscopic resection of esophageal cancer requires long-term post-op surveillance
LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.
Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.
“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”
To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.
After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.
CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.
Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.
“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”
Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.
“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”
Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.
“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”
The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.
“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”
The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.
LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.
Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.
“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”
To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.
After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.
CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.
Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.
“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”
Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.
“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”
Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.
“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”
The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.
“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”
The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.
LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.
Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.
“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”
To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.
After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.
CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.
Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.
“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”
Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.
“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”
Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.
“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”
The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.
“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”
The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.
FROM ACG 2021
People of color missing in inflammatory bowel disease trials
LAS VEGAS – Clinical trials of treatments for inflammatory bowel disease (IBD) have disproportionately enrolled White people, researchers say.
These skewed demographics could result in researchers overlooking differences in how the disease and its treatments might affect other racial and ethnic groups, said Jellyana Peraza, MD, a chief resident at Albert Einstein College of Medicine, New York.
“The only way we can determine that therapies work differently in different populations is by including those populations in these clinical trials,” she said in an interview. “We think that diversity should be present, and that will answer some questions about the pathogenesis of the disease in general.”
Dr. Peraza presented the findings at the annual meeting of the American College of Gastroenterology.
Previous studies have found that, in trials of other conditions, such as cancer and cardiovascular disease, White people have been disproportionately represented. However, little research has been conducted regarding race and ethnicity in IBD trials.
To fill that gap, Dr. Peraza and colleagues analyzed data from completed trials through the U.S. National Library of Medicine’s registry, ClinicalTrials.gov, for the period from 2000 to 2020.
They found 22 trials conducted exclusively in the United States and 56 conducted in other countries that reported the race or ethnicity of participants; 54 trials did not include this information.
With regard to the prevalence of IBD in White people and Asian people, these populations were overrepresented in U.S. clinical trials. All other groups were underrepresented.
The researchers calculated the odds ratio of being included in an IBD clinical trial for each group. Compared with White people, all the other groups were less likely to be included except for Asian people, who were 85% more likely to be included. These ORs were all statistically significant (P < .03) except for Hispanic people (OR, 0.81; 95% confidence interval, 0.65-1.01; P = .06).
It’s not clear why Asian people are overrepresented, Dr. Peraza said. “Honestly, that was kind of surprising for us. We initially thought that could be related to where these studies were conducted, for example, if some of them were conducted on the West Coast, where maybe more Asian communities are located. However, we didn’t find any specific association between location and Asian representation.”
IBD is more prevalent among White people, although its prevalence is increasing among other groups, Dr. Peraza said. However, that is not reflected in the trials. In an analysis of data in 5-year increments, the researchers found that the participation of White and Hispanic people in IBD trials had not changed much, whereas the participation of Black people had declined, and the participation of Asian and Native American people had increased.
On the basis of work of other researchers, Dr. Peraza said that people of color are as willing to participate in trials as White people. “There is not so much a mistrust as a lack of education and a lack of access to the tertiary centers or the centers where these studies are conducted,” she said.
Clinical trial investigators should recruit more participants from community centers, and health care practitioners should talk about the trials with people in underrepresented groups, she said. “They should have the conversation with their patients about how these clinical trials can benefit the evolution of their diseases.”
One research center that is working hard to diversify its IBD trials is the Ohio State University IBD Center, Columbus, said Anita Afzali, MD, its medical director.
“We have a great team that works actively on the recruitment of all patients,” she said in an interview. “Oftentimes, it just takes a little bit of education and spending time with the patient on discussing what the options are for them.”
Some research indicates that Black people with IBD are more likely to have fistulizing disease, Dr. Afzali said. “However, it doesn’t come so much of their differences in phenotype that we’re seeing but more so the differences in access to care and getting the appropriate therapy in a timely way.”
Dr. Peraza and Dr. Afzali disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LAS VEGAS – Clinical trials of treatments for inflammatory bowel disease (IBD) have disproportionately enrolled White people, researchers say.
These skewed demographics could result in researchers overlooking differences in how the disease and its treatments might affect other racial and ethnic groups, said Jellyana Peraza, MD, a chief resident at Albert Einstein College of Medicine, New York.
“The only way we can determine that therapies work differently in different populations is by including those populations in these clinical trials,” she said in an interview. “We think that diversity should be present, and that will answer some questions about the pathogenesis of the disease in general.”
Dr. Peraza presented the findings at the annual meeting of the American College of Gastroenterology.
Previous studies have found that, in trials of other conditions, such as cancer and cardiovascular disease, White people have been disproportionately represented. However, little research has been conducted regarding race and ethnicity in IBD trials.
To fill that gap, Dr. Peraza and colleagues analyzed data from completed trials through the U.S. National Library of Medicine’s registry, ClinicalTrials.gov, for the period from 2000 to 2020.
They found 22 trials conducted exclusively in the United States and 56 conducted in other countries that reported the race or ethnicity of participants; 54 trials did not include this information.
With regard to the prevalence of IBD in White people and Asian people, these populations were overrepresented in U.S. clinical trials. All other groups were underrepresented.
The researchers calculated the odds ratio of being included in an IBD clinical trial for each group. Compared with White people, all the other groups were less likely to be included except for Asian people, who were 85% more likely to be included. These ORs were all statistically significant (P < .03) except for Hispanic people (OR, 0.81; 95% confidence interval, 0.65-1.01; P = .06).
It’s not clear why Asian people are overrepresented, Dr. Peraza said. “Honestly, that was kind of surprising for us. We initially thought that could be related to where these studies were conducted, for example, if some of them were conducted on the West Coast, where maybe more Asian communities are located. However, we didn’t find any specific association between location and Asian representation.”
IBD is more prevalent among White people, although its prevalence is increasing among other groups, Dr. Peraza said. However, that is not reflected in the trials. In an analysis of data in 5-year increments, the researchers found that the participation of White and Hispanic people in IBD trials had not changed much, whereas the participation of Black people had declined, and the participation of Asian and Native American people had increased.
On the basis of work of other researchers, Dr. Peraza said that people of color are as willing to participate in trials as White people. “There is not so much a mistrust as a lack of education and a lack of access to the tertiary centers or the centers where these studies are conducted,” she said.
Clinical trial investigators should recruit more participants from community centers, and health care practitioners should talk about the trials with people in underrepresented groups, she said. “They should have the conversation with their patients about how these clinical trials can benefit the evolution of their diseases.”
One research center that is working hard to diversify its IBD trials is the Ohio State University IBD Center, Columbus, said Anita Afzali, MD, its medical director.
“We have a great team that works actively on the recruitment of all patients,” she said in an interview. “Oftentimes, it just takes a little bit of education and spending time with the patient on discussing what the options are for them.”
Some research indicates that Black people with IBD are more likely to have fistulizing disease, Dr. Afzali said. “However, it doesn’t come so much of their differences in phenotype that we’re seeing but more so the differences in access to care and getting the appropriate therapy in a timely way.”
Dr. Peraza and Dr. Afzali disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LAS VEGAS – Clinical trials of treatments for inflammatory bowel disease (IBD) have disproportionately enrolled White people, researchers say.
These skewed demographics could result in researchers overlooking differences in how the disease and its treatments might affect other racial and ethnic groups, said Jellyana Peraza, MD, a chief resident at Albert Einstein College of Medicine, New York.
“The only way we can determine that therapies work differently in different populations is by including those populations in these clinical trials,” she said in an interview. “We think that diversity should be present, and that will answer some questions about the pathogenesis of the disease in general.”
Dr. Peraza presented the findings at the annual meeting of the American College of Gastroenterology.
Previous studies have found that, in trials of other conditions, such as cancer and cardiovascular disease, White people have been disproportionately represented. However, little research has been conducted regarding race and ethnicity in IBD trials.
To fill that gap, Dr. Peraza and colleagues analyzed data from completed trials through the U.S. National Library of Medicine’s registry, ClinicalTrials.gov, for the period from 2000 to 2020.
They found 22 trials conducted exclusively in the United States and 56 conducted in other countries that reported the race or ethnicity of participants; 54 trials did not include this information.
With regard to the prevalence of IBD in White people and Asian people, these populations were overrepresented in U.S. clinical trials. All other groups were underrepresented.
The researchers calculated the odds ratio of being included in an IBD clinical trial for each group. Compared with White people, all the other groups were less likely to be included except for Asian people, who were 85% more likely to be included. These ORs were all statistically significant (P < .03) except for Hispanic people (OR, 0.81; 95% confidence interval, 0.65-1.01; P = .06).
It’s not clear why Asian people are overrepresented, Dr. Peraza said. “Honestly, that was kind of surprising for us. We initially thought that could be related to where these studies were conducted, for example, if some of them were conducted on the West Coast, where maybe more Asian communities are located. However, we didn’t find any specific association between location and Asian representation.”
IBD is more prevalent among White people, although its prevalence is increasing among other groups, Dr. Peraza said. However, that is not reflected in the trials. In an analysis of data in 5-year increments, the researchers found that the participation of White and Hispanic people in IBD trials had not changed much, whereas the participation of Black people had declined, and the participation of Asian and Native American people had increased.
On the basis of work of other researchers, Dr. Peraza said that people of color are as willing to participate in trials as White people. “There is not so much a mistrust as a lack of education and a lack of access to the tertiary centers or the centers where these studies are conducted,” she said.
Clinical trial investigators should recruit more participants from community centers, and health care practitioners should talk about the trials with people in underrepresented groups, she said. “They should have the conversation with their patients about how these clinical trials can benefit the evolution of their diseases.”
One research center that is working hard to diversify its IBD trials is the Ohio State University IBD Center, Columbus, said Anita Afzali, MD, its medical director.
“We have a great team that works actively on the recruitment of all patients,” she said in an interview. “Oftentimes, it just takes a little bit of education and spending time with the patient on discussing what the options are for them.”
Some research indicates that Black people with IBD are more likely to have fistulizing disease, Dr. Afzali said. “However, it doesn’t come so much of their differences in phenotype that we’re seeing but more so the differences in access to care and getting the appropriate therapy in a timely way.”
Dr. Peraza and Dr. Afzali disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACG 2021
In diabetes, fast-growing pancreatic cysts may be a red flag
LAS VEGAS – New results from a single center, retrospective analysis suggest that individuals with diabetes and pancreatic cysts have larger cyst sizes at diagnosis, and a faster subsequent cyst growth rate. Smoking was independently associated with faster growth rate.
Most pancreatic cancer patients were previously diagnosed with hyperglycemia and diabetes, and pancreatic cancer can cause diabetes. “This sort of dual causality raises questions as to whether or not hyperglycemia, or the new diagnosis of diabetes itself, could be a harbinger of cancer or precancer. And should these patients be more closely monitored?” David Robbins, MD, said in an interview.
Dr. Robbins, associate professor of medicine and program director in gastroenterology in the Northwell Health System, New York, presented the study at the annual meeting of the American College of Gastroenterology.
Faster growth rates of pancreatic cysts in the presence of diabetes are important because they represent a potential mark for cyst aggressiveness. “So the question really is, in the setting of diabetes, are there factors perhaps circulating in the bloodstream, or other intrinsic factors, that make these cysts more dangerous and require a different surveillance approach than someone who doesn’t have diabetes? We have (surveillance) guidelines that address the average population, but they don’t really hone in on what do you do with (individuals with diabetes),” Dr. Robbins said during the presentation.
The study could have implications for screening, said session moderator Dayna Early, MD, professor of medicine at Washington University and director of endoscopy at Barnes Jewish Hospital, both in St. Louis. “I think this is important information to guide us to look more closely at patients with diabetes who do have pancreatic cysts,” she said in an interview.
The study included 177 adults with pancreatic cysts or abnormal imaging results between 2013 and 2020. Sixty-five percent were female, and the mean age was 65.4 years; 64% were White, 10% were Black, and 8.5% were Asian. Among the participants, 24.8% were smokers and 32.2% had type 2 diabetes.
Patients with diabetes had larger cyst sizes (2.23 cm versus 2.76 cm), as well as a higher annual cyst growth rate (1.90 cm versus 1.30 cm). Cyst size and growth rate were similar between patients with controlled and uncontrolled diabetes. Smoking was associated with a larger cyst size overall (2.2 cm versus 1.81 cm), and were larger still among patients with diabetes who smoked (2.35 cm).
Seventy-one patients went on to have pathologic confirmation by endoscopic ultrasound-guided fine needle aspiration. “In the diabetic group, two developed adenocarcinoma, six of the nondiabetics developed adenocarcinoma, and there was no difference in CEA or serum CA 19-9,” Dr. Robbins said during his presentation.
Of 28 patients diagnosed with pancreatic cancer, 13 had type 2 diabetes.
Defining danger
There remains uncertainty about what cyst growth rate is most dangerous. Some guidelines recommend that individuals with new-onset or worsening diabetes and intraductal papillary mucinous neoplasm or mucinous cystic neoplasm cysts, or cysts alone that are growing faster than 3 mm per year, may be at significantly increased risk of pancreatic cancer. These guidelines recommend that they be screened with short-interval magnetic resonance imaging or endoscopic ultrasound (EUS) fine needle aspiration. However, this recommendation is conditional and is backed by a very low level of evidence.
Other reports have shown varying risks at different growth rates. “It’s not really clear at this point. And that’s why I think, while our study is small and exploratory, this is a particular area that is relatively easy to evaluate. We have huge databases of pancreatic cyst evolution, and we know that 30 million Americans have diabetes. So, the next obvious study is to do a more systematic look at that, and work towards refining and making sense of these divergent guidelines, all of which are saying the same thing but using different threshold numbers,” said Dr. Robbins.
The next step is do larger, multicenter studies in the context of other risk factors such as family history and smoking, but the current finding represents an opportunity to catch at least some pancreatic cancers earlier, according to Dr. Robbins. He suggested that individuals with diabetes who are diagnosed with a pancreatic cyst should be referred to a gastroenterologist or another specialist to track cyst growth. “That is going to miss a lot of folks who didn’t get imaging for whatever reason (and so don’t have a cyst identified), but it is an early opportunity, and it’s better than what we’re doing now.”
During the talk, Dr. Robbins said, “Given the ease, availability and low cost of diabetes screening in the general clinic population, we encourage the inclusion of HbA1c and fasting glucose in algorithms for pancreatic cyst surveillance.”
Dr. Early found the suggestion intriguing, but wasn’t ready to lend full support. “I think looking at the suggestion of possibly monitoring hemoglobin A1c levels was novel. I don’t know that we’ll necessarily adopt that as standard practice, but that’s something I think that could be looked at in the future as a way to help risk stratify whether patients need to be surveyed more frequently,” she said.
Dr. Robbins and Dr. Early have no relevant financial disclosures.
LAS VEGAS – New results from a single center, retrospective analysis suggest that individuals with diabetes and pancreatic cysts have larger cyst sizes at diagnosis, and a faster subsequent cyst growth rate. Smoking was independently associated with faster growth rate.
Most pancreatic cancer patients were previously diagnosed with hyperglycemia and diabetes, and pancreatic cancer can cause diabetes. “This sort of dual causality raises questions as to whether or not hyperglycemia, or the new diagnosis of diabetes itself, could be a harbinger of cancer or precancer. And should these patients be more closely monitored?” David Robbins, MD, said in an interview.
Dr. Robbins, associate professor of medicine and program director in gastroenterology in the Northwell Health System, New York, presented the study at the annual meeting of the American College of Gastroenterology.
Faster growth rates of pancreatic cysts in the presence of diabetes are important because they represent a potential mark for cyst aggressiveness. “So the question really is, in the setting of diabetes, are there factors perhaps circulating in the bloodstream, or other intrinsic factors, that make these cysts more dangerous and require a different surveillance approach than someone who doesn’t have diabetes? We have (surveillance) guidelines that address the average population, but they don’t really hone in on what do you do with (individuals with diabetes),” Dr. Robbins said during the presentation.
The study could have implications for screening, said session moderator Dayna Early, MD, professor of medicine at Washington University and director of endoscopy at Barnes Jewish Hospital, both in St. Louis. “I think this is important information to guide us to look more closely at patients with diabetes who do have pancreatic cysts,” she said in an interview.
The study included 177 adults with pancreatic cysts or abnormal imaging results between 2013 and 2020. Sixty-five percent were female, and the mean age was 65.4 years; 64% were White, 10% were Black, and 8.5% were Asian. Among the participants, 24.8% were smokers and 32.2% had type 2 diabetes.
Patients with diabetes had larger cyst sizes (2.23 cm versus 2.76 cm), as well as a higher annual cyst growth rate (1.90 cm versus 1.30 cm). Cyst size and growth rate were similar between patients with controlled and uncontrolled diabetes. Smoking was associated with a larger cyst size overall (2.2 cm versus 1.81 cm), and were larger still among patients with diabetes who smoked (2.35 cm).
Seventy-one patients went on to have pathologic confirmation by endoscopic ultrasound-guided fine needle aspiration. “In the diabetic group, two developed adenocarcinoma, six of the nondiabetics developed adenocarcinoma, and there was no difference in CEA or serum CA 19-9,” Dr. Robbins said during his presentation.
Of 28 patients diagnosed with pancreatic cancer, 13 had type 2 diabetes.
Defining danger
There remains uncertainty about what cyst growth rate is most dangerous. Some guidelines recommend that individuals with new-onset or worsening diabetes and intraductal papillary mucinous neoplasm or mucinous cystic neoplasm cysts, or cysts alone that are growing faster than 3 mm per year, may be at significantly increased risk of pancreatic cancer. These guidelines recommend that they be screened with short-interval magnetic resonance imaging or endoscopic ultrasound (EUS) fine needle aspiration. However, this recommendation is conditional and is backed by a very low level of evidence.
Other reports have shown varying risks at different growth rates. “It’s not really clear at this point. And that’s why I think, while our study is small and exploratory, this is a particular area that is relatively easy to evaluate. We have huge databases of pancreatic cyst evolution, and we know that 30 million Americans have diabetes. So, the next obvious study is to do a more systematic look at that, and work towards refining and making sense of these divergent guidelines, all of which are saying the same thing but using different threshold numbers,” said Dr. Robbins.
The next step is do larger, multicenter studies in the context of other risk factors such as family history and smoking, but the current finding represents an opportunity to catch at least some pancreatic cancers earlier, according to Dr. Robbins. He suggested that individuals with diabetes who are diagnosed with a pancreatic cyst should be referred to a gastroenterologist or another specialist to track cyst growth. “That is going to miss a lot of folks who didn’t get imaging for whatever reason (and so don’t have a cyst identified), but it is an early opportunity, and it’s better than what we’re doing now.”
During the talk, Dr. Robbins said, “Given the ease, availability and low cost of diabetes screening in the general clinic population, we encourage the inclusion of HbA1c and fasting glucose in algorithms for pancreatic cyst surveillance.”
Dr. Early found the suggestion intriguing, but wasn’t ready to lend full support. “I think looking at the suggestion of possibly monitoring hemoglobin A1c levels was novel. I don’t know that we’ll necessarily adopt that as standard practice, but that’s something I think that could be looked at in the future as a way to help risk stratify whether patients need to be surveyed more frequently,” she said.
Dr. Robbins and Dr. Early have no relevant financial disclosures.
LAS VEGAS – New results from a single center, retrospective analysis suggest that individuals with diabetes and pancreatic cysts have larger cyst sizes at diagnosis, and a faster subsequent cyst growth rate. Smoking was independently associated with faster growth rate.
Most pancreatic cancer patients were previously diagnosed with hyperglycemia and diabetes, and pancreatic cancer can cause diabetes. “This sort of dual causality raises questions as to whether or not hyperglycemia, or the new diagnosis of diabetes itself, could be a harbinger of cancer or precancer. And should these patients be more closely monitored?” David Robbins, MD, said in an interview.
Dr. Robbins, associate professor of medicine and program director in gastroenterology in the Northwell Health System, New York, presented the study at the annual meeting of the American College of Gastroenterology.
Faster growth rates of pancreatic cysts in the presence of diabetes are important because they represent a potential mark for cyst aggressiveness. “So the question really is, in the setting of diabetes, are there factors perhaps circulating in the bloodstream, or other intrinsic factors, that make these cysts more dangerous and require a different surveillance approach than someone who doesn’t have diabetes? We have (surveillance) guidelines that address the average population, but they don’t really hone in on what do you do with (individuals with diabetes),” Dr. Robbins said during the presentation.
The study could have implications for screening, said session moderator Dayna Early, MD, professor of medicine at Washington University and director of endoscopy at Barnes Jewish Hospital, both in St. Louis. “I think this is important information to guide us to look more closely at patients with diabetes who do have pancreatic cysts,” she said in an interview.
The study included 177 adults with pancreatic cysts or abnormal imaging results between 2013 and 2020. Sixty-five percent were female, and the mean age was 65.4 years; 64% were White, 10% were Black, and 8.5% were Asian. Among the participants, 24.8% were smokers and 32.2% had type 2 diabetes.
Patients with diabetes had larger cyst sizes (2.23 cm versus 2.76 cm), as well as a higher annual cyst growth rate (1.90 cm versus 1.30 cm). Cyst size and growth rate were similar between patients with controlled and uncontrolled diabetes. Smoking was associated with a larger cyst size overall (2.2 cm versus 1.81 cm), and were larger still among patients with diabetes who smoked (2.35 cm).
Seventy-one patients went on to have pathologic confirmation by endoscopic ultrasound-guided fine needle aspiration. “In the diabetic group, two developed adenocarcinoma, six of the nondiabetics developed adenocarcinoma, and there was no difference in CEA or serum CA 19-9,” Dr. Robbins said during his presentation.
Of 28 patients diagnosed with pancreatic cancer, 13 had type 2 diabetes.
Defining danger
There remains uncertainty about what cyst growth rate is most dangerous. Some guidelines recommend that individuals with new-onset or worsening diabetes and intraductal papillary mucinous neoplasm or mucinous cystic neoplasm cysts, or cysts alone that are growing faster than 3 mm per year, may be at significantly increased risk of pancreatic cancer. These guidelines recommend that they be screened with short-interval magnetic resonance imaging or endoscopic ultrasound (EUS) fine needle aspiration. However, this recommendation is conditional and is backed by a very low level of evidence.
Other reports have shown varying risks at different growth rates. “It’s not really clear at this point. And that’s why I think, while our study is small and exploratory, this is a particular area that is relatively easy to evaluate. We have huge databases of pancreatic cyst evolution, and we know that 30 million Americans have diabetes. So, the next obvious study is to do a more systematic look at that, and work towards refining and making sense of these divergent guidelines, all of which are saying the same thing but using different threshold numbers,” said Dr. Robbins.
The next step is do larger, multicenter studies in the context of other risk factors such as family history and smoking, but the current finding represents an opportunity to catch at least some pancreatic cancers earlier, according to Dr. Robbins. He suggested that individuals with diabetes who are diagnosed with a pancreatic cyst should be referred to a gastroenterologist or another specialist to track cyst growth. “That is going to miss a lot of folks who didn’t get imaging for whatever reason (and so don’t have a cyst identified), but it is an early opportunity, and it’s better than what we’re doing now.”
During the talk, Dr. Robbins said, “Given the ease, availability and low cost of diabetes screening in the general clinic population, we encourage the inclusion of HbA1c and fasting glucose in algorithms for pancreatic cyst surveillance.”
Dr. Early found the suggestion intriguing, but wasn’t ready to lend full support. “I think looking at the suggestion of possibly monitoring hemoglobin A1c levels was novel. I don’t know that we’ll necessarily adopt that as standard practice, but that’s something I think that could be looked at in the future as a way to help risk stratify whether patients need to be surveyed more frequently,” she said.
Dr. Robbins and Dr. Early have no relevant financial disclosures.
AT ACG 2021
Upadacitinib delivers rapid response in ulcerative colitis
Induction therapy with Janus kinase inhibitor upadacitinib is superior to placebo for patients with moderately to severely active ulcerative colitis (UC), regardless of prior biologic treatments, based on results of the phase 3 U-ACHIEVE trial.
Clinical responses in the upadacitinib group occurred as soon as 2 weeks and were sustained through the 8-week study period, reported lead author Silvio Danese, MD, PhD, of Humanitas Clinical and Research Center IRCCS and Hunimed, Milan.
“Despite availability of multiple treatment options, many patients with ulcerative colitis do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease,” said coauthor Peter Higgins, MD, PhD, of the University of Michigan, Ann Arbor, who presented findings at the annual meeting of the American College of Gastroenterology.
The U-ACHIEVE trial involved 474 patients with moderate to severe UC randomized to receive either upadacitinib induction therapy (45 mg once daily; n = 319) or placebo (n = 155). The primary endpoint was clinical remission at week 8. Secondary endpoints included endoscopic improvement at week 8, endoscopic remission at week 8, clinical response at week 8, clinical response at week 2, histologic-endoscopic mucosal improvement at week 8, and adverse events.
The study population was “very sick” and “very experienced,” Dr. Higgins said, noting that approximately half of the patients had inadequate responses to prior biologics, and within this subgroup of inadequate responders, approximately two-thirds of the patients had received more than one prior biologic. According to Dr. Higgins, this helps explain why 12.3% of the patients in the placebo group discontinued therapy, compared with just 3.8% in the upadacitinib group – because most patients involved were “quite ill.”
At week 8, 26.1% of the patients in the upadacitinib group had achieved clinical remission, versus 4.8% of the patients given placebo (26.1% vs. 4.8%; P < .0001). Clinical response at week 2 followed a similar pattern (60.1% vs. 27.3%; P < .001), as did clinical response at week 8 (72.6% vs. 27.3%; P < .0001).
All other 8-week secondary endpoints also significantly favored upadacitinib, including endoscopic improvement (36.3% vs 7.4%), endoscopic remission (13.7% vs 1.3%), and histologic-endoscopic mucosal improvement (29.9% vs. 6.5%).
Serious and severe adverse events were more common in the placebo group, and patients in the placebo group more frequently discontinued therapy because of treatment-related adverse events. While rates of serious infection were similar between groups, patients taking upadacitinib had higher rates of neutropenia and lymphopenia.
Based on these findings, the investigators concluded that upadacitinib induction therapy is superior to placebo for clinical remission and clinical response regardless of previous treatment failure.
According to Jordan E. Axelrad, MD, of New York University Langone Health, the findings reflect a real-world setting and clinicians should take note of the rapid response observed with upadacitinib.
“This was a relatively sick group, so you know this reflects what we’re seeing in clinical practice,” Dr. Axelrad said in an interview. “Clinical response was detected as early week 2, and that’s extremely important to highlight, because a lot of our drugs that we have on the market – some of these biologics – may take a little time to work. Having a drug that can work fast and is effective is critical.”
Dr. Axelrad suggested that second-line JAK inhibitors like upadacitinib, which target JAK proteins more selectively than first-generation agents, may alleviate some lingering concerns about JAK inhibitor safety; still, optimal treatment sequencing remains unclear.
“With more selective inhibition, you’re getting less of that side-effect profile,” Dr. Axelrad said, noting that long-term data is needed to confirm this likelihood. “The real question moving forward is: Will upadacitinib replace first-generation JAK inhibitors as a category, or, because of the broader safety profile, will it come earlier in the positioning of where we put our drugs for colitis?”
Dr. Axelrad suggested that the answer may ultimately come from regulators, although patients could also guide decision-making.
“Oral drugs are a really important mode of administration that we’re missing for the moderate to severe group,” he said. “Should [further clinical trials] demonstrate superior safety to nonselective JAK inhibitors, upadacitinib could be a first-line option for patients who don’t want to be taking an infusion or injection, more especially so for those that are already biologically experienced, or need something fast.”
Siddharth Singh, MD, director of the IBD Center at the University of California, San Diego, called U-ACHIEVE a “pivotal trial” that demonstrated the “remarkable efficacy” of upadacitinib for moderate to severe ulcerative colitis; still, he noted that drug sequencing remains undetermined.
“It’s unclear whether or not it’ll be the best in class for JAK inhibitors right now,” Dr. Singh said in an interview. “A lot of that hinges on the safety of this drug. In terms of positioning, it depends on whether the [Food and Drug Administration] requires patients to have failed anti–[tumor necrosis factor] therapy before using this drug, like tofacitinib.”
That may depend on long-term data, he suggested.
“Right now, it is hard to comment on the relative safety of upadacitinib versus tofacitinib,” Dr. Singh said. “While the JAK1 selectivity may contribute to efficacy by allowing us to use a higher dose, it’s unclear whether the higher dose of this medication is any safer than tofacitinib. Longer term, 5- to 7-year registry studies of real-world data are warranted to examine risk of cardiovascular disease, thromboembolism, malignancy, and mortality with upadacitinib.
“How to sequence and position these therapies in real-world practice is a key question,” he concluded.
The study was supported by AbbVie. The investigators disclosed additional affiliations with Genentech, Ferring, AstraZeneca, and others. Dr. Axelrad has previously consulted for AbbVie. Dr. Singh has received research funding from AbbVie, Pfizer, and Janssen in the last 24 months, as well as personal fees from Pfizer for an ad hoc grant review.
Induction therapy with Janus kinase inhibitor upadacitinib is superior to placebo for patients with moderately to severely active ulcerative colitis (UC), regardless of prior biologic treatments, based on results of the phase 3 U-ACHIEVE trial.
Clinical responses in the upadacitinib group occurred as soon as 2 weeks and were sustained through the 8-week study period, reported lead author Silvio Danese, MD, PhD, of Humanitas Clinical and Research Center IRCCS and Hunimed, Milan.
“Despite availability of multiple treatment options, many patients with ulcerative colitis do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease,” said coauthor Peter Higgins, MD, PhD, of the University of Michigan, Ann Arbor, who presented findings at the annual meeting of the American College of Gastroenterology.
The U-ACHIEVE trial involved 474 patients with moderate to severe UC randomized to receive either upadacitinib induction therapy (45 mg once daily; n = 319) or placebo (n = 155). The primary endpoint was clinical remission at week 8. Secondary endpoints included endoscopic improvement at week 8, endoscopic remission at week 8, clinical response at week 8, clinical response at week 2, histologic-endoscopic mucosal improvement at week 8, and adverse events.
The study population was “very sick” and “very experienced,” Dr. Higgins said, noting that approximately half of the patients had inadequate responses to prior biologics, and within this subgroup of inadequate responders, approximately two-thirds of the patients had received more than one prior biologic. According to Dr. Higgins, this helps explain why 12.3% of the patients in the placebo group discontinued therapy, compared with just 3.8% in the upadacitinib group – because most patients involved were “quite ill.”
At week 8, 26.1% of the patients in the upadacitinib group had achieved clinical remission, versus 4.8% of the patients given placebo (26.1% vs. 4.8%; P < .0001). Clinical response at week 2 followed a similar pattern (60.1% vs. 27.3%; P < .001), as did clinical response at week 8 (72.6% vs. 27.3%; P < .0001).
All other 8-week secondary endpoints also significantly favored upadacitinib, including endoscopic improvement (36.3% vs 7.4%), endoscopic remission (13.7% vs 1.3%), and histologic-endoscopic mucosal improvement (29.9% vs. 6.5%).
Serious and severe adverse events were more common in the placebo group, and patients in the placebo group more frequently discontinued therapy because of treatment-related adverse events. While rates of serious infection were similar between groups, patients taking upadacitinib had higher rates of neutropenia and lymphopenia.
Based on these findings, the investigators concluded that upadacitinib induction therapy is superior to placebo for clinical remission and clinical response regardless of previous treatment failure.
According to Jordan E. Axelrad, MD, of New York University Langone Health, the findings reflect a real-world setting and clinicians should take note of the rapid response observed with upadacitinib.
“This was a relatively sick group, so you know this reflects what we’re seeing in clinical practice,” Dr. Axelrad said in an interview. “Clinical response was detected as early week 2, and that’s extremely important to highlight, because a lot of our drugs that we have on the market – some of these biologics – may take a little time to work. Having a drug that can work fast and is effective is critical.”
Dr. Axelrad suggested that second-line JAK inhibitors like upadacitinib, which target JAK proteins more selectively than first-generation agents, may alleviate some lingering concerns about JAK inhibitor safety; still, optimal treatment sequencing remains unclear.
“With more selective inhibition, you’re getting less of that side-effect profile,” Dr. Axelrad said, noting that long-term data is needed to confirm this likelihood. “The real question moving forward is: Will upadacitinib replace first-generation JAK inhibitors as a category, or, because of the broader safety profile, will it come earlier in the positioning of where we put our drugs for colitis?”
Dr. Axelrad suggested that the answer may ultimately come from regulators, although patients could also guide decision-making.
“Oral drugs are a really important mode of administration that we’re missing for the moderate to severe group,” he said. “Should [further clinical trials] demonstrate superior safety to nonselective JAK inhibitors, upadacitinib could be a first-line option for patients who don’t want to be taking an infusion or injection, more especially so for those that are already biologically experienced, or need something fast.”
Siddharth Singh, MD, director of the IBD Center at the University of California, San Diego, called U-ACHIEVE a “pivotal trial” that demonstrated the “remarkable efficacy” of upadacitinib for moderate to severe ulcerative colitis; still, he noted that drug sequencing remains undetermined.
“It’s unclear whether or not it’ll be the best in class for JAK inhibitors right now,” Dr. Singh said in an interview. “A lot of that hinges on the safety of this drug. In terms of positioning, it depends on whether the [Food and Drug Administration] requires patients to have failed anti–[tumor necrosis factor] therapy before using this drug, like tofacitinib.”
That may depend on long-term data, he suggested.
“Right now, it is hard to comment on the relative safety of upadacitinib versus tofacitinib,” Dr. Singh said. “While the JAK1 selectivity may contribute to efficacy by allowing us to use a higher dose, it’s unclear whether the higher dose of this medication is any safer than tofacitinib. Longer term, 5- to 7-year registry studies of real-world data are warranted to examine risk of cardiovascular disease, thromboembolism, malignancy, and mortality with upadacitinib.
“How to sequence and position these therapies in real-world practice is a key question,” he concluded.
The study was supported by AbbVie. The investigators disclosed additional affiliations with Genentech, Ferring, AstraZeneca, and others. Dr. Axelrad has previously consulted for AbbVie. Dr. Singh has received research funding from AbbVie, Pfizer, and Janssen in the last 24 months, as well as personal fees from Pfizer for an ad hoc grant review.
Induction therapy with Janus kinase inhibitor upadacitinib is superior to placebo for patients with moderately to severely active ulcerative colitis (UC), regardless of prior biologic treatments, based on results of the phase 3 U-ACHIEVE trial.
Clinical responses in the upadacitinib group occurred as soon as 2 weeks and were sustained through the 8-week study period, reported lead author Silvio Danese, MD, PhD, of Humanitas Clinical and Research Center IRCCS and Hunimed, Milan.
“Despite availability of multiple treatment options, many patients with ulcerative colitis do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease,” said coauthor Peter Higgins, MD, PhD, of the University of Michigan, Ann Arbor, who presented findings at the annual meeting of the American College of Gastroenterology.
The U-ACHIEVE trial involved 474 patients with moderate to severe UC randomized to receive either upadacitinib induction therapy (45 mg once daily; n = 319) or placebo (n = 155). The primary endpoint was clinical remission at week 8. Secondary endpoints included endoscopic improvement at week 8, endoscopic remission at week 8, clinical response at week 8, clinical response at week 2, histologic-endoscopic mucosal improvement at week 8, and adverse events.
The study population was “very sick” and “very experienced,” Dr. Higgins said, noting that approximately half of the patients had inadequate responses to prior biologics, and within this subgroup of inadequate responders, approximately two-thirds of the patients had received more than one prior biologic. According to Dr. Higgins, this helps explain why 12.3% of the patients in the placebo group discontinued therapy, compared with just 3.8% in the upadacitinib group – because most patients involved were “quite ill.”
At week 8, 26.1% of the patients in the upadacitinib group had achieved clinical remission, versus 4.8% of the patients given placebo (26.1% vs. 4.8%; P < .0001). Clinical response at week 2 followed a similar pattern (60.1% vs. 27.3%; P < .001), as did clinical response at week 8 (72.6% vs. 27.3%; P < .0001).
All other 8-week secondary endpoints also significantly favored upadacitinib, including endoscopic improvement (36.3% vs 7.4%), endoscopic remission (13.7% vs 1.3%), and histologic-endoscopic mucosal improvement (29.9% vs. 6.5%).
Serious and severe adverse events were more common in the placebo group, and patients in the placebo group more frequently discontinued therapy because of treatment-related adverse events. While rates of serious infection were similar between groups, patients taking upadacitinib had higher rates of neutropenia and lymphopenia.
Based on these findings, the investigators concluded that upadacitinib induction therapy is superior to placebo for clinical remission and clinical response regardless of previous treatment failure.
According to Jordan E. Axelrad, MD, of New York University Langone Health, the findings reflect a real-world setting and clinicians should take note of the rapid response observed with upadacitinib.
“This was a relatively sick group, so you know this reflects what we’re seeing in clinical practice,” Dr. Axelrad said in an interview. “Clinical response was detected as early week 2, and that’s extremely important to highlight, because a lot of our drugs that we have on the market – some of these biologics – may take a little time to work. Having a drug that can work fast and is effective is critical.”
Dr. Axelrad suggested that second-line JAK inhibitors like upadacitinib, which target JAK proteins more selectively than first-generation agents, may alleviate some lingering concerns about JAK inhibitor safety; still, optimal treatment sequencing remains unclear.
“With more selective inhibition, you’re getting less of that side-effect profile,” Dr. Axelrad said, noting that long-term data is needed to confirm this likelihood. “The real question moving forward is: Will upadacitinib replace first-generation JAK inhibitors as a category, or, because of the broader safety profile, will it come earlier in the positioning of where we put our drugs for colitis?”
Dr. Axelrad suggested that the answer may ultimately come from regulators, although patients could also guide decision-making.
“Oral drugs are a really important mode of administration that we’re missing for the moderate to severe group,” he said. “Should [further clinical trials] demonstrate superior safety to nonselective JAK inhibitors, upadacitinib could be a first-line option for patients who don’t want to be taking an infusion or injection, more especially so for those that are already biologically experienced, or need something fast.”
Siddharth Singh, MD, director of the IBD Center at the University of California, San Diego, called U-ACHIEVE a “pivotal trial” that demonstrated the “remarkable efficacy” of upadacitinib for moderate to severe ulcerative colitis; still, he noted that drug sequencing remains undetermined.
“It’s unclear whether or not it’ll be the best in class for JAK inhibitors right now,” Dr. Singh said in an interview. “A lot of that hinges on the safety of this drug. In terms of positioning, it depends on whether the [Food and Drug Administration] requires patients to have failed anti–[tumor necrosis factor] therapy before using this drug, like tofacitinib.”
That may depend on long-term data, he suggested.
“Right now, it is hard to comment on the relative safety of upadacitinib versus tofacitinib,” Dr. Singh said. “While the JAK1 selectivity may contribute to efficacy by allowing us to use a higher dose, it’s unclear whether the higher dose of this medication is any safer than tofacitinib. Longer term, 5- to 7-year registry studies of real-world data are warranted to examine risk of cardiovascular disease, thromboembolism, malignancy, and mortality with upadacitinib.
“How to sequence and position these therapies in real-world practice is a key question,” he concluded.
The study was supported by AbbVie. The investigators disclosed additional affiliations with Genentech, Ferring, AstraZeneca, and others. Dr. Axelrad has previously consulted for AbbVie. Dr. Singh has received research funding from AbbVie, Pfizer, and Janssen in the last 24 months, as well as personal fees from Pfizer for an ad hoc grant review.
FROM ACG 2021
Automated duodenoscope cleaner clears out contamination
LAS VEGAS – An automated cleaning system outperformed manual cleaning of duodenoscopes in a comparative study. The results included measurements of residual proteins and carbohydrates in all duodenoscope working channels and elevators.
The new automated cleaning system, called the MACH 1, can be added to existing reprocessing areas and is about the size of a commercial washing machine. Cleaning alone takes about 30 minutes, and clean plus high-level disinfection (HLD) takes about an hour, according to Michael O’Donnell, MD, who is a gastroenterology fellow at NYU Langone Health. “Data from prior studies of other automated endoscope reprocessors indicate that MACH 1 more consistently delivers cleaning results that meet or exceed Food and Drug Administration/AAMI (Association for the Advancement of Medical Instrumentation) guidelines,” Dr. O’Donnell said in an interview. He presented the study at the annual meeting of the American College of Gastroenterology.
Outbreaks of multidrug resistant organism (MDRO) transmission have been linked to inadequately cleaned duodenoscopes, which has led to greater attention being paid to duodenoscope reprocessing, including prewash, manual cleaning, and disinfection or sterilization, according to Dr. O’Donnell. Postmarketing surveillance by duodenoscope manufacturers Fujifilm, Olympus, and Pentax found a contamination rate of 5.4% for any high-concern organisms – far higher than the initially assumed 0.4%.
The researchers used FDA standard maximum allowed contaminant threshold of < 6.4 mcg/cm2 protein and < 2.2 mcg/cm2 carbohydrate. Sampling sites on the duodenoscopes included the elevator wire channel port when present, the biopsy port, the elevator wire channel, the instrument channel, and the elevator recess.
The study included Olympic TJF-Q180V duodenoscopes used in 48 endoscopic retrograde cholangiopancreatography (ERCP) procedures. Each instrument went through standard bedside precleaning; 21 were then cleaned manually by trained technicians following manufacturing instructions, and 27 were cleaned using the automated cleaning system.
In the manually cleaned duodenoscopes, the average level of residual protein was 4.88 mcg/cm2, versus 0.16 mcg/cm2 in the automated clean group. The average carbohydrate residues were 1.09 mcg/cm2 and 0.14 mcg/cm2, respectively. In all, 2 of the 21 manually cleaned devices had protein levels higher than the FDA threshold, versus none in the automated clean group. In addition, 3 of 21 in the manually cleaned group had higher than threshold carbohydrate levels, versus none in the automated clean group. Overall, 4 of the 27 manually cleaned devices and none of the 21 automated clean devices had protein or carbohydrate levels above FDA thresholds.
Removing variability from cleaning
The cleaning step is critical because failure to remove bioburden can reduce the efficacy of later HLD or sterilization. Cleaning is typically done manually, but the physical complexity of the duodenoscope makes it challenging to do it thoroughly. Manual cleaning is also susceptible to human error or insufficient training, and an observational study found that at least one error occurred in more than 90% of observed cleaning operations.
The MACH 1 uses turbulent flow and resultant shearing forces to clean the duodenoscope. The device is currently used at the medical device company Parametrik as part of a program that delivers clean duodenoscopes and ultrasound scopes to its customers. The service is currently available only in the New York metro area, but the company intends to expand to other cities in 2022. The company also has plans to sell the MACH 1 in the near future at prices comparable to automated endoscope reprocessors that don’t clean, according to Dr. O’Donnell.
“This is a huge issue, not only practically for patient care, but it’s very much in the public eye. As people who do ERCP, this is a question that patients will come to us with, so we want to be as diligent as possible to drive the bioburden in the scope as low as we can. At least intuitively, that makes sense,” said Patrick Young, MD, who comoderated the session and is a professor of medicine at the Uniformed Services University, Bethesda, Md.
He noted that the system has an advantage in that it can be applied to duodenoscopes already in house. Other approaches to the issue of improperly cleaned duodenoscopes include scopes that can be returned to the manufacturer for cleaning, or removable end cap to facilitate access to difficult to clean parts. And then there are disposal duodenoscopes. “If you’re throwing a scope away every time you use it, you worry about landfill issues and some of the long term effects of that,” said Dr. Young.
Perhaps the most important attribute of the automated cleaning device is that it allows the user to eliminate variation in the cleaning procedure. High-reliability organizations aspire to eliminating variability. “This will probably make it easier to be consistent across technicians – for example, maybe there’s one tech that cleans great and one tech that doesn’t. This may take some of that out of the equation and give you a more thorough cleaning regardless of circumstance or personnel working on it. So I think it’s exciting to have another option that might be less costly than buying new scopes,” said Dr. Young.
Dr. O’Donnell and Dr. Young have no relevant financial disclosures.
LAS VEGAS – An automated cleaning system outperformed manual cleaning of duodenoscopes in a comparative study. The results included measurements of residual proteins and carbohydrates in all duodenoscope working channels and elevators.
The new automated cleaning system, called the MACH 1, can be added to existing reprocessing areas and is about the size of a commercial washing machine. Cleaning alone takes about 30 minutes, and clean plus high-level disinfection (HLD) takes about an hour, according to Michael O’Donnell, MD, who is a gastroenterology fellow at NYU Langone Health. “Data from prior studies of other automated endoscope reprocessors indicate that MACH 1 more consistently delivers cleaning results that meet or exceed Food and Drug Administration/AAMI (Association for the Advancement of Medical Instrumentation) guidelines,” Dr. O’Donnell said in an interview. He presented the study at the annual meeting of the American College of Gastroenterology.
Outbreaks of multidrug resistant organism (MDRO) transmission have been linked to inadequately cleaned duodenoscopes, which has led to greater attention being paid to duodenoscope reprocessing, including prewash, manual cleaning, and disinfection or sterilization, according to Dr. O’Donnell. Postmarketing surveillance by duodenoscope manufacturers Fujifilm, Olympus, and Pentax found a contamination rate of 5.4% for any high-concern organisms – far higher than the initially assumed 0.4%.
The researchers used FDA standard maximum allowed contaminant threshold of < 6.4 mcg/cm2 protein and < 2.2 mcg/cm2 carbohydrate. Sampling sites on the duodenoscopes included the elevator wire channel port when present, the biopsy port, the elevator wire channel, the instrument channel, and the elevator recess.
The study included Olympic TJF-Q180V duodenoscopes used in 48 endoscopic retrograde cholangiopancreatography (ERCP) procedures. Each instrument went through standard bedside precleaning; 21 were then cleaned manually by trained technicians following manufacturing instructions, and 27 were cleaned using the automated cleaning system.
In the manually cleaned duodenoscopes, the average level of residual protein was 4.88 mcg/cm2, versus 0.16 mcg/cm2 in the automated clean group. The average carbohydrate residues were 1.09 mcg/cm2 and 0.14 mcg/cm2, respectively. In all, 2 of the 21 manually cleaned devices had protein levels higher than the FDA threshold, versus none in the automated clean group. In addition, 3 of 21 in the manually cleaned group had higher than threshold carbohydrate levels, versus none in the automated clean group. Overall, 4 of the 27 manually cleaned devices and none of the 21 automated clean devices had protein or carbohydrate levels above FDA thresholds.
Removing variability from cleaning
The cleaning step is critical because failure to remove bioburden can reduce the efficacy of later HLD or sterilization. Cleaning is typically done manually, but the physical complexity of the duodenoscope makes it challenging to do it thoroughly. Manual cleaning is also susceptible to human error or insufficient training, and an observational study found that at least one error occurred in more than 90% of observed cleaning operations.
The MACH 1 uses turbulent flow and resultant shearing forces to clean the duodenoscope. The device is currently used at the medical device company Parametrik as part of a program that delivers clean duodenoscopes and ultrasound scopes to its customers. The service is currently available only in the New York metro area, but the company intends to expand to other cities in 2022. The company also has plans to sell the MACH 1 in the near future at prices comparable to automated endoscope reprocessors that don’t clean, according to Dr. O’Donnell.
“This is a huge issue, not only practically for patient care, but it’s very much in the public eye. As people who do ERCP, this is a question that patients will come to us with, so we want to be as diligent as possible to drive the bioburden in the scope as low as we can. At least intuitively, that makes sense,” said Patrick Young, MD, who comoderated the session and is a professor of medicine at the Uniformed Services University, Bethesda, Md.
He noted that the system has an advantage in that it can be applied to duodenoscopes already in house. Other approaches to the issue of improperly cleaned duodenoscopes include scopes that can be returned to the manufacturer for cleaning, or removable end cap to facilitate access to difficult to clean parts. And then there are disposal duodenoscopes. “If you’re throwing a scope away every time you use it, you worry about landfill issues and some of the long term effects of that,” said Dr. Young.
Perhaps the most important attribute of the automated cleaning device is that it allows the user to eliminate variation in the cleaning procedure. High-reliability organizations aspire to eliminating variability. “This will probably make it easier to be consistent across technicians – for example, maybe there’s one tech that cleans great and one tech that doesn’t. This may take some of that out of the equation and give you a more thorough cleaning regardless of circumstance or personnel working on it. So I think it’s exciting to have another option that might be less costly than buying new scopes,” said Dr. Young.
Dr. O’Donnell and Dr. Young have no relevant financial disclosures.
LAS VEGAS – An automated cleaning system outperformed manual cleaning of duodenoscopes in a comparative study. The results included measurements of residual proteins and carbohydrates in all duodenoscope working channels and elevators.
The new automated cleaning system, called the MACH 1, can be added to existing reprocessing areas and is about the size of a commercial washing machine. Cleaning alone takes about 30 minutes, and clean plus high-level disinfection (HLD) takes about an hour, according to Michael O’Donnell, MD, who is a gastroenterology fellow at NYU Langone Health. “Data from prior studies of other automated endoscope reprocessors indicate that MACH 1 more consistently delivers cleaning results that meet or exceed Food and Drug Administration/AAMI (Association for the Advancement of Medical Instrumentation) guidelines,” Dr. O’Donnell said in an interview. He presented the study at the annual meeting of the American College of Gastroenterology.
Outbreaks of multidrug resistant organism (MDRO) transmission have been linked to inadequately cleaned duodenoscopes, which has led to greater attention being paid to duodenoscope reprocessing, including prewash, manual cleaning, and disinfection or sterilization, according to Dr. O’Donnell. Postmarketing surveillance by duodenoscope manufacturers Fujifilm, Olympus, and Pentax found a contamination rate of 5.4% for any high-concern organisms – far higher than the initially assumed 0.4%.
The researchers used FDA standard maximum allowed contaminant threshold of < 6.4 mcg/cm2 protein and < 2.2 mcg/cm2 carbohydrate. Sampling sites on the duodenoscopes included the elevator wire channel port when present, the biopsy port, the elevator wire channel, the instrument channel, and the elevator recess.
The study included Olympic TJF-Q180V duodenoscopes used in 48 endoscopic retrograde cholangiopancreatography (ERCP) procedures. Each instrument went through standard bedside precleaning; 21 were then cleaned manually by trained technicians following manufacturing instructions, and 27 were cleaned using the automated cleaning system.
In the manually cleaned duodenoscopes, the average level of residual protein was 4.88 mcg/cm2, versus 0.16 mcg/cm2 in the automated clean group. The average carbohydrate residues were 1.09 mcg/cm2 and 0.14 mcg/cm2, respectively. In all, 2 of the 21 manually cleaned devices had protein levels higher than the FDA threshold, versus none in the automated clean group. In addition, 3 of 21 in the manually cleaned group had higher than threshold carbohydrate levels, versus none in the automated clean group. Overall, 4 of the 27 manually cleaned devices and none of the 21 automated clean devices had protein or carbohydrate levels above FDA thresholds.
Removing variability from cleaning
The cleaning step is critical because failure to remove bioburden can reduce the efficacy of later HLD or sterilization. Cleaning is typically done manually, but the physical complexity of the duodenoscope makes it challenging to do it thoroughly. Manual cleaning is also susceptible to human error or insufficient training, and an observational study found that at least one error occurred in more than 90% of observed cleaning operations.
The MACH 1 uses turbulent flow and resultant shearing forces to clean the duodenoscope. The device is currently used at the medical device company Parametrik as part of a program that delivers clean duodenoscopes and ultrasound scopes to its customers. The service is currently available only in the New York metro area, but the company intends to expand to other cities in 2022. The company also has plans to sell the MACH 1 in the near future at prices comparable to automated endoscope reprocessors that don’t clean, according to Dr. O’Donnell.
“This is a huge issue, not only practically for patient care, but it’s very much in the public eye. As people who do ERCP, this is a question that patients will come to us with, so we want to be as diligent as possible to drive the bioburden in the scope as low as we can. At least intuitively, that makes sense,” said Patrick Young, MD, who comoderated the session and is a professor of medicine at the Uniformed Services University, Bethesda, Md.
He noted that the system has an advantage in that it can be applied to duodenoscopes already in house. Other approaches to the issue of improperly cleaned duodenoscopes include scopes that can be returned to the manufacturer for cleaning, or removable end cap to facilitate access to difficult to clean parts. And then there are disposal duodenoscopes. “If you’re throwing a scope away every time you use it, you worry about landfill issues and some of the long term effects of that,” said Dr. Young.
Perhaps the most important attribute of the automated cleaning device is that it allows the user to eliminate variation in the cleaning procedure. High-reliability organizations aspire to eliminating variability. “This will probably make it easier to be consistent across technicians – for example, maybe there’s one tech that cleans great and one tech that doesn’t. This may take some of that out of the equation and give you a more thorough cleaning regardless of circumstance or personnel working on it. So I think it’s exciting to have another option that might be less costly than buying new scopes,” said Dr. Young.
Dr. O’Donnell and Dr. Young have no relevant financial disclosures.
AT ACG 2021
Alcohol-related liver disease severity increased during COVID-19 pandemic
LAS VEGAS – Over the course of the COVID-19 pandemic, alcohol-related liver disease has increased in severity, a finding that is likely related to higher consumption of alcohol and reduced care. The difference was notable in higher Model for End-Stage Liver Disease–sodium (MELD-Na) scores, more signs of hepatic decompensation, and higher mortality rates.
“Alcohol consumption during the COVID-19 pandemic led to increased morbidity and mortality, specifically in patients that already had underlying liver disease. The importance of alcohol cessation, counseling, and close physician monitoring is emphasized, given continued or relapsed alcohol consumption can significantly affect quality of life, life expectancy, and liver transplantation candidacy,” research team member Lindsay A. Sobotka, DO, said in an interview. Dr. Sobotka is an assistant professor of gastroenterology, hepatology, and nutrition at the Ohio State University Wexner Medical Center, Columbus.
The research was presented by Ayushi Jain, MD, at the annual meeting of the American College of Gastroenterology. Dr. Jain is a resident at the Ohio State University Wexner Medical Center.
Dr. Jain noted that alcohol sales have gone up during the pandemic, with monthly sales up 14%-44% between February and September 2020, compared with the same months in previous years.
Decompensation rates rose
The researchers analyzed data from patients with alcoholic cirrhosis or alcoholic hepatitis who were seen at the Ohio State University Medical Center between March and August 2019, and between March and August 2020.
During the pandemic, the number of hospital admissions nearly doubled among alcoholic hepatitis patients (86 to 162), but declined slightly among patients with alcoholic cirrhosis (613 to 528), possibly because of efforts to manage decompensation and avoid hospitalizations during the pandemic, according to Dr. Jain. In total, 4 of 162 patients with alcoholic hepatitis and 14 of 528 patients with alcoholic cirrhosis had COVID-19 at the time of admission.
Higher mortality rates were seen during the pandemic, although this was only significant for alcoholic cirrhosis: 14.8% versus 7% for alcoholic hepatitis (P = .06) and 13.5% versus 7.4% for alcoholic cirrhosis (P = .001).
Among those with alcoholic hepatitis, there was no significant change in median Maddrey’s Discriminant Function during the pandemic (P = .51), but the researchers noted a significant decrease in steroid use, from 27 patients to 23 (P = .001). “This may be due to a statistically significant increase in GI bleeds and renal dysfunction that we noted during the pandemic,” said Dr. Jain.
Hepatic decompensation and critical care needs increased among patients admitted with alcoholic hepatitis, including hepatic encephalopathy (P = .037), gastrointestinal bleeding (P = .01), a need for increased oxygen (P = .024), vasopressor support (P = .005), and initiation of hemodialysis (P = .007). The median highest MELD-Na score during admission was also higher during the pandemic (24 vs. 23, P = .04).
Patients with alcoholic cirrhosis had greater decompensation as measured by ascites (P = .01), therapeutic paracentesis (P = .04), titration of diuretics (P = .005), acute kidney injury (P = .005), hepatorenal syndrome (P = .002), and spontaneous bacterial peritonitis (P = .04). They also had greater need for vasopressor support (9% to 14%; P = .006), were more likely to initiate hemodialysis (7% to 11%; P = .015), and had greater mortality (7% to 14%; P = .001).
In all, 212 patients reported increased alcohol intake, 161 reported little change over the past year, and 253 said they were abstinent. MELD-Na scores were highest in the increased group (27), compared with the unchanged group (24) and abstinent group (23) (P = .001).
More robust support needed
“This highlights that the increase in alcohol use seems to be associated with higher rates of more severe alcoholic hepatitis, and we are going to need to all be aware of and intervene in these individuals, and try to not only make health care more accessible, but help those with alcohol use disorder to reengage in some support systems [and] harm-reduction measures, to try to reduce the number of these episodes of admissions with severe alcoholic hepatitis,” said Paul Kwo, MD, who comoderated the session. Dr. Kwo is a professor of medicine at Stanford (Calif.) University.
Dr. Kwo suggested that the pandemic has presented dual challenges to patients with alcohol-related liver disease. One is that hospitals have filled up because of an influx of COVID-19 cases, which makes it hard for them to compete for limited resources. The other is that lockdowns and social interruptions may have interfered with the support systems that normally help them to keep sober and maintain health care. “The pandemic really disrupted everybody’s ecosystem substantially, and some of these individuals, as their ecosystems crumble, they don’t have other resources to engage in care, and then they present with far more advanced comorbidities than we might have seen prior to the pandemic,” said Dr. Kwo.
The findings underscore at least one lesson that can be drawn from the pandemic. “We now know that we have to develop more robust systems to provide support for all of these individuals,” said Dr. Kwo.
Comoderator Patricia D. Jones, MD, agreed, and expressed optimism. “We were forced develop more remote or virtual networks, so I think there are a lot of people that are taking advantage maybe of virtual [Alcoholics Anonymous], and that wasn’t something that they necessarily did [before the pandemic]. And so at least we’ve developed some parallel systems that hopefully people will benefit from,” said Dr. Jones, who is an assistant professor of medicine at the University of Miami.
She suggested that physicians should make inquiries about patients with alcohol-related liver disease and their social situations, and might consider trying to connect them to a social worker if called for. “I think that really speaking to the person about where they are would be beneficial,” said Dr. Jones.
Dr. Sobotka, Dr. Jain, Dr. Kwo, and Dr. Jones have no relevant financial disclosures.
LAS VEGAS – Over the course of the COVID-19 pandemic, alcohol-related liver disease has increased in severity, a finding that is likely related to higher consumption of alcohol and reduced care. The difference was notable in higher Model for End-Stage Liver Disease–sodium (MELD-Na) scores, more signs of hepatic decompensation, and higher mortality rates.
“Alcohol consumption during the COVID-19 pandemic led to increased morbidity and mortality, specifically in patients that already had underlying liver disease. The importance of alcohol cessation, counseling, and close physician monitoring is emphasized, given continued or relapsed alcohol consumption can significantly affect quality of life, life expectancy, and liver transplantation candidacy,” research team member Lindsay A. Sobotka, DO, said in an interview. Dr. Sobotka is an assistant professor of gastroenterology, hepatology, and nutrition at the Ohio State University Wexner Medical Center, Columbus.
The research was presented by Ayushi Jain, MD, at the annual meeting of the American College of Gastroenterology. Dr. Jain is a resident at the Ohio State University Wexner Medical Center.
Dr. Jain noted that alcohol sales have gone up during the pandemic, with monthly sales up 14%-44% between February and September 2020, compared with the same months in previous years.
Decompensation rates rose
The researchers analyzed data from patients with alcoholic cirrhosis or alcoholic hepatitis who were seen at the Ohio State University Medical Center between March and August 2019, and between March and August 2020.
During the pandemic, the number of hospital admissions nearly doubled among alcoholic hepatitis patients (86 to 162), but declined slightly among patients with alcoholic cirrhosis (613 to 528), possibly because of efforts to manage decompensation and avoid hospitalizations during the pandemic, according to Dr. Jain. In total, 4 of 162 patients with alcoholic hepatitis and 14 of 528 patients with alcoholic cirrhosis had COVID-19 at the time of admission.
Higher mortality rates were seen during the pandemic, although this was only significant for alcoholic cirrhosis: 14.8% versus 7% for alcoholic hepatitis (P = .06) and 13.5% versus 7.4% for alcoholic cirrhosis (P = .001).
Among those with alcoholic hepatitis, there was no significant change in median Maddrey’s Discriminant Function during the pandemic (P = .51), but the researchers noted a significant decrease in steroid use, from 27 patients to 23 (P = .001). “This may be due to a statistically significant increase in GI bleeds and renal dysfunction that we noted during the pandemic,” said Dr. Jain.
Hepatic decompensation and critical care needs increased among patients admitted with alcoholic hepatitis, including hepatic encephalopathy (P = .037), gastrointestinal bleeding (P = .01), a need for increased oxygen (P = .024), vasopressor support (P = .005), and initiation of hemodialysis (P = .007). The median highest MELD-Na score during admission was also higher during the pandemic (24 vs. 23, P = .04).
Patients with alcoholic cirrhosis had greater decompensation as measured by ascites (P = .01), therapeutic paracentesis (P = .04), titration of diuretics (P = .005), acute kidney injury (P = .005), hepatorenal syndrome (P = .002), and spontaneous bacterial peritonitis (P = .04). They also had greater need for vasopressor support (9% to 14%; P = .006), were more likely to initiate hemodialysis (7% to 11%; P = .015), and had greater mortality (7% to 14%; P = .001).
In all, 212 patients reported increased alcohol intake, 161 reported little change over the past year, and 253 said they were abstinent. MELD-Na scores were highest in the increased group (27), compared with the unchanged group (24) and abstinent group (23) (P = .001).
More robust support needed
“This highlights that the increase in alcohol use seems to be associated with higher rates of more severe alcoholic hepatitis, and we are going to need to all be aware of and intervene in these individuals, and try to not only make health care more accessible, but help those with alcohol use disorder to reengage in some support systems [and] harm-reduction measures, to try to reduce the number of these episodes of admissions with severe alcoholic hepatitis,” said Paul Kwo, MD, who comoderated the session. Dr. Kwo is a professor of medicine at Stanford (Calif.) University.
Dr. Kwo suggested that the pandemic has presented dual challenges to patients with alcohol-related liver disease. One is that hospitals have filled up because of an influx of COVID-19 cases, which makes it hard for them to compete for limited resources. The other is that lockdowns and social interruptions may have interfered with the support systems that normally help them to keep sober and maintain health care. “The pandemic really disrupted everybody’s ecosystem substantially, and some of these individuals, as their ecosystems crumble, they don’t have other resources to engage in care, and then they present with far more advanced comorbidities than we might have seen prior to the pandemic,” said Dr. Kwo.
The findings underscore at least one lesson that can be drawn from the pandemic. “We now know that we have to develop more robust systems to provide support for all of these individuals,” said Dr. Kwo.
Comoderator Patricia D. Jones, MD, agreed, and expressed optimism. “We were forced develop more remote or virtual networks, so I think there are a lot of people that are taking advantage maybe of virtual [Alcoholics Anonymous], and that wasn’t something that they necessarily did [before the pandemic]. And so at least we’ve developed some parallel systems that hopefully people will benefit from,” said Dr. Jones, who is an assistant professor of medicine at the University of Miami.
She suggested that physicians should make inquiries about patients with alcohol-related liver disease and their social situations, and might consider trying to connect them to a social worker if called for. “I think that really speaking to the person about where they are would be beneficial,” said Dr. Jones.
Dr. Sobotka, Dr. Jain, Dr. Kwo, and Dr. Jones have no relevant financial disclosures.
LAS VEGAS – Over the course of the COVID-19 pandemic, alcohol-related liver disease has increased in severity, a finding that is likely related to higher consumption of alcohol and reduced care. The difference was notable in higher Model for End-Stage Liver Disease–sodium (MELD-Na) scores, more signs of hepatic decompensation, and higher mortality rates.
“Alcohol consumption during the COVID-19 pandemic led to increased morbidity and mortality, specifically in patients that already had underlying liver disease. The importance of alcohol cessation, counseling, and close physician monitoring is emphasized, given continued or relapsed alcohol consumption can significantly affect quality of life, life expectancy, and liver transplantation candidacy,” research team member Lindsay A. Sobotka, DO, said in an interview. Dr. Sobotka is an assistant professor of gastroenterology, hepatology, and nutrition at the Ohio State University Wexner Medical Center, Columbus.
The research was presented by Ayushi Jain, MD, at the annual meeting of the American College of Gastroenterology. Dr. Jain is a resident at the Ohio State University Wexner Medical Center.
Dr. Jain noted that alcohol sales have gone up during the pandemic, with monthly sales up 14%-44% between February and September 2020, compared with the same months in previous years.
Decompensation rates rose
The researchers analyzed data from patients with alcoholic cirrhosis or alcoholic hepatitis who were seen at the Ohio State University Medical Center between March and August 2019, and between March and August 2020.
During the pandemic, the number of hospital admissions nearly doubled among alcoholic hepatitis patients (86 to 162), but declined slightly among patients with alcoholic cirrhosis (613 to 528), possibly because of efforts to manage decompensation and avoid hospitalizations during the pandemic, according to Dr. Jain. In total, 4 of 162 patients with alcoholic hepatitis and 14 of 528 patients with alcoholic cirrhosis had COVID-19 at the time of admission.
Higher mortality rates were seen during the pandemic, although this was only significant for alcoholic cirrhosis: 14.8% versus 7% for alcoholic hepatitis (P = .06) and 13.5% versus 7.4% for alcoholic cirrhosis (P = .001).
Among those with alcoholic hepatitis, there was no significant change in median Maddrey’s Discriminant Function during the pandemic (P = .51), but the researchers noted a significant decrease in steroid use, from 27 patients to 23 (P = .001). “This may be due to a statistically significant increase in GI bleeds and renal dysfunction that we noted during the pandemic,” said Dr. Jain.
Hepatic decompensation and critical care needs increased among patients admitted with alcoholic hepatitis, including hepatic encephalopathy (P = .037), gastrointestinal bleeding (P = .01), a need for increased oxygen (P = .024), vasopressor support (P = .005), and initiation of hemodialysis (P = .007). The median highest MELD-Na score during admission was also higher during the pandemic (24 vs. 23, P = .04).
Patients with alcoholic cirrhosis had greater decompensation as measured by ascites (P = .01), therapeutic paracentesis (P = .04), titration of diuretics (P = .005), acute kidney injury (P = .005), hepatorenal syndrome (P = .002), and spontaneous bacterial peritonitis (P = .04). They also had greater need for vasopressor support (9% to 14%; P = .006), were more likely to initiate hemodialysis (7% to 11%; P = .015), and had greater mortality (7% to 14%; P = .001).
In all, 212 patients reported increased alcohol intake, 161 reported little change over the past year, and 253 said they were abstinent. MELD-Na scores were highest in the increased group (27), compared with the unchanged group (24) and abstinent group (23) (P = .001).
More robust support needed
“This highlights that the increase in alcohol use seems to be associated with higher rates of more severe alcoholic hepatitis, and we are going to need to all be aware of and intervene in these individuals, and try to not only make health care more accessible, but help those with alcohol use disorder to reengage in some support systems [and] harm-reduction measures, to try to reduce the number of these episodes of admissions with severe alcoholic hepatitis,” said Paul Kwo, MD, who comoderated the session. Dr. Kwo is a professor of medicine at Stanford (Calif.) University.
Dr. Kwo suggested that the pandemic has presented dual challenges to patients with alcohol-related liver disease. One is that hospitals have filled up because of an influx of COVID-19 cases, which makes it hard for them to compete for limited resources. The other is that lockdowns and social interruptions may have interfered with the support systems that normally help them to keep sober and maintain health care. “The pandemic really disrupted everybody’s ecosystem substantially, and some of these individuals, as their ecosystems crumble, they don’t have other resources to engage in care, and then they present with far more advanced comorbidities than we might have seen prior to the pandemic,” said Dr. Kwo.
The findings underscore at least one lesson that can be drawn from the pandemic. “We now know that we have to develop more robust systems to provide support for all of these individuals,” said Dr. Kwo.
Comoderator Patricia D. Jones, MD, agreed, and expressed optimism. “We were forced develop more remote or virtual networks, so I think there are a lot of people that are taking advantage maybe of virtual [Alcoholics Anonymous], and that wasn’t something that they necessarily did [before the pandemic]. And so at least we’ve developed some parallel systems that hopefully people will benefit from,” said Dr. Jones, who is an assistant professor of medicine at the University of Miami.
She suggested that physicians should make inquiries about patients with alcohol-related liver disease and their social situations, and might consider trying to connect them to a social worker if called for. “I think that really speaking to the person about where they are would be beneficial,” said Dr. Jones.
Dr. Sobotka, Dr. Jain, Dr. Kwo, and Dr. Jones have no relevant financial disclosures.
AT ACG 2021
Risankizumab has early and lasting benefits in Crohn’s disease
LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.
Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.
“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”
Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.
Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.
A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
MOTIVATE and ADVANCE studies
The two induction trials for Crohn’s disease enrolled slightly different populations.
The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.
The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.
In both trials, intravenous injections were given at weeks 0, 4, and 8.
The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.
A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.
At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.
By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.
In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.
“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
FORTIFY study
In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.
At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)
“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.
Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.
There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.
Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.
A version of this article first appeared on Medscape.com.
LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.
Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.
“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”
Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.
Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.
A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
MOTIVATE and ADVANCE studies
The two induction trials for Crohn’s disease enrolled slightly different populations.
The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.
The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.
In both trials, intravenous injections were given at weeks 0, 4, and 8.
The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.
A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.
At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.
By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.
In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.
“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
FORTIFY study
In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.
At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)
“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.
Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.
There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.
Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.
A version of this article first appeared on Medscape.com.
LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.
Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.
“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”
Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.
Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.
A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
MOTIVATE and ADVANCE studies
The two induction trials for Crohn’s disease enrolled slightly different populations.
The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.
The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.
In both trials, intravenous injections were given at weeks 0, 4, and 8.
The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.
A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.
At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.
By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.
In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.
“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
FORTIFY study
In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.
At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)
“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.
Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.
There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.
Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.
A version of this article first appeared on Medscape.com.
AT ACG 2021
Obesity interventions tied to colon cancer risk reduction
LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.
“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.
Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.
Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.
Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.
They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).
Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.
They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.
For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.
In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.
They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m2 who did not undergo weight loss surgery or take weight loss medication.
Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).
On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).
All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).
The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.
While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”
As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.
Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.
“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”
Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.
The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.
“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.
Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.
Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.
Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.
They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).
Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.
They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.
For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.
In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.
They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m2 who did not undergo weight loss surgery or take weight loss medication.
Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).
On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).
All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).
The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.
While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”
As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.
Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.
“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”
Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.
The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.
“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.
Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.
Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.
Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.
They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).
Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.
They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.
For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.
In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.
They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m2 who did not undergo weight loss surgery or take weight loss medication.
Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).
On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).
All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).
The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.
While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”
As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.
Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.
“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”
Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.
The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACG 2021
Upadacitinib shows potential for ulcerative colitis
LAS VEGAS – An oral Janus kinase 1 inhibitor upadacitinib (Rinvoq, AbbVie) showed high efficacy and good safety as a treatment for ulcerative colitis in a phase 3 trial.
The finding could provide some reassurance after the Food and Drug Administration recently warned of an increased risk of cancer and heart disease associated with medications in the same class as upadacitinib.
“Serious adverse events were numerically lower in patients on upadacitinib, and discontinuations from the study due to adverse events were also lower” than in patients taking a placebo, said Edward Loftus, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
Dr. Loftus presented the findings from the U-ACCOMPLISH study at the annual meeting of the American College of Gastroenterology.
Although other medications are approved for the treatment of ulcerative colitis, including biologics, many patients do not respond. In 2019, tofacitinib (Xeljanz) became the first JAK inhibitor approved for this condition. It works by blocking the JAK1 and JAK3 inflammation pathways, and at high concentrations, it also blocks the tyrosine kinase 2 and JAK2 pathways.
However, adverse events seen in clinical trials of tofacitinib include pneumonia, herpes zoster, anal abscess, and Clostridioides difficile infections. And, as reported by this news organization in September, the FDA required its manufacturer, Pfizer, to add a boxed warning that includes information about the risks of stroke, cancer, blood clots, and death.
Upadacitinib may be more selective and reversible because it preferentially blocks JAK1 or JAK1/3. In August 2019, it received FDA approval at a dose of 15 mg for adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.
But the FDA applied the same warnings to upadacitinib – and to a third related drug, baricitinib (Olumiant) – that it required for tofacitinib, even though they are not as well studied.
The FDA also limited approved uses of these three medications to patients who have not responded well to tumor necrosis factor blockers to ensure their benefits outweigh their risks.
A well-tolerated treatment
U-ACCOMPLISH is one of two phase 3 trials induction trials completed on upadacitinib.
Investigators randomized 522 people with moderately to severely active ulcerative colitis, defined as Adapted Mayo Score 5-9 with a centrally read endoscopic score of 2-3. Of those patients, the intent to treat population included 341 in the upadacitinib group (45 mg once daily) and 174 in the placebo group.
The baseline demographics and disease characteristics were similar between groups. More than two-thirds of patients in both groups were White, and more than two-thirds were men. In the upadacitinib group, 50.7% had responded inadequately to biologic treatments, compared with 51.1% in the placebo group.
After 8 weeks, a significantly higher proportion of patients receiving upadacitinib achieved clinical remission as defined by the adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1).
“In terms of the efficacy, I think it’s very, very promising,” said Derrick Eichele, MD, an assistant professor of gastroenterology-hepatology at the University of Nebraska Medical Center in Omaha, who was not involved in the trial.
The efficacy data were similar to those reported for tofacitinib in clinical trials, he said in an interview. “But I think again, what we’re waiting to see is how is this going to be positioned in relation to tofacitinib in terms of safety profile.”
More patients in the upadacitinib group reported adverse events, including those deemed related to the drug. However, the proportion that were severe, serious, or led to discontinuation was higher in the placebo group. No one in the study died, and no one in the upadacitinib group had an adjudicated major adverse cardiovascular event, tuberculosis, or malignancy.
The most common adverse events were acne, blood creatine phosphokinase elevation, and anemia, which were all more common in the upadacitinib group, and headache and worsening of ulcerative colitis, which were more common in the placebo group.
Among adverse events of special interest, anemia, neutropenia, hepatic disorder, lymphopenia, serious infection, and opportunistic infection were more common in the upadacitinib group than in the placebo group. The four opportunistic infections in the upadacitinib group included two cases of herpes zoster.
In reviewing the poster presented at this meeting, the cases of neutropenia and hepatic disorder in the upadacitinib group stood out for Dr. Eichele. But he said it’s hard to pass judgment based on this amount of data. He is looking forward to a peer-reviewed publication. “I’ll be interested to see what it shows in terms of the details.”
Phase 3 trials of upadacitinib are underway in atopic dermatitis, RA, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, and Takayasu arteritis as well as ulcerative colitis.
In a 52-week maintenance trial, according to a press release, malignancies (excluding nonmelanoma skin cancer) included one event among 148 people taking a 15-mg dose of upadacitinib 15, two events among 154 people taking a 30-mg dose of upadacitinib, and one event among 149 people in the placebo group.
Two cases of pulmonary embolism were reported in the 15-mg group and two cases of deep vein thrombosis were reported in the 30-mg group, compared with one event of ovarian vein thrombosis in the placebo group. One adjudicated major cardiovascular event each were reported in the upadacitinib 30-mg group and the placebo group. No one died.
The study was funded by AbbVie. Dr. Loftus reported that he is a consultant for AbbVie as well as multiple other gastroenterology drug companies. Dr. Eichele disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LAS VEGAS – An oral Janus kinase 1 inhibitor upadacitinib (Rinvoq, AbbVie) showed high efficacy and good safety as a treatment for ulcerative colitis in a phase 3 trial.
The finding could provide some reassurance after the Food and Drug Administration recently warned of an increased risk of cancer and heart disease associated with medications in the same class as upadacitinib.
“Serious adverse events were numerically lower in patients on upadacitinib, and discontinuations from the study due to adverse events were also lower” than in patients taking a placebo, said Edward Loftus, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
Dr. Loftus presented the findings from the U-ACCOMPLISH study at the annual meeting of the American College of Gastroenterology.
Although other medications are approved for the treatment of ulcerative colitis, including biologics, many patients do not respond. In 2019, tofacitinib (Xeljanz) became the first JAK inhibitor approved for this condition. It works by blocking the JAK1 and JAK3 inflammation pathways, and at high concentrations, it also blocks the tyrosine kinase 2 and JAK2 pathways.
However, adverse events seen in clinical trials of tofacitinib include pneumonia, herpes zoster, anal abscess, and Clostridioides difficile infections. And, as reported by this news organization in September, the FDA required its manufacturer, Pfizer, to add a boxed warning that includes information about the risks of stroke, cancer, blood clots, and death.
Upadacitinib may be more selective and reversible because it preferentially blocks JAK1 or JAK1/3. In August 2019, it received FDA approval at a dose of 15 mg for adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.
But the FDA applied the same warnings to upadacitinib – and to a third related drug, baricitinib (Olumiant) – that it required for tofacitinib, even though they are not as well studied.
The FDA also limited approved uses of these three medications to patients who have not responded well to tumor necrosis factor blockers to ensure their benefits outweigh their risks.
A well-tolerated treatment
U-ACCOMPLISH is one of two phase 3 trials induction trials completed on upadacitinib.
Investigators randomized 522 people with moderately to severely active ulcerative colitis, defined as Adapted Mayo Score 5-9 with a centrally read endoscopic score of 2-3. Of those patients, the intent to treat population included 341 in the upadacitinib group (45 mg once daily) and 174 in the placebo group.
The baseline demographics and disease characteristics were similar between groups. More than two-thirds of patients in both groups were White, and more than two-thirds were men. In the upadacitinib group, 50.7% had responded inadequately to biologic treatments, compared with 51.1% in the placebo group.
After 8 weeks, a significantly higher proportion of patients receiving upadacitinib achieved clinical remission as defined by the adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1).
“In terms of the efficacy, I think it’s very, very promising,” said Derrick Eichele, MD, an assistant professor of gastroenterology-hepatology at the University of Nebraska Medical Center in Omaha, who was not involved in the trial.
The efficacy data were similar to those reported for tofacitinib in clinical trials, he said in an interview. “But I think again, what we’re waiting to see is how is this going to be positioned in relation to tofacitinib in terms of safety profile.”
More patients in the upadacitinib group reported adverse events, including those deemed related to the drug. However, the proportion that were severe, serious, or led to discontinuation was higher in the placebo group. No one in the study died, and no one in the upadacitinib group had an adjudicated major adverse cardiovascular event, tuberculosis, or malignancy.
The most common adverse events were acne, blood creatine phosphokinase elevation, and anemia, which were all more common in the upadacitinib group, and headache and worsening of ulcerative colitis, which were more common in the placebo group.
Among adverse events of special interest, anemia, neutropenia, hepatic disorder, lymphopenia, serious infection, and opportunistic infection were more common in the upadacitinib group than in the placebo group. The four opportunistic infections in the upadacitinib group included two cases of herpes zoster.
In reviewing the poster presented at this meeting, the cases of neutropenia and hepatic disorder in the upadacitinib group stood out for Dr. Eichele. But he said it’s hard to pass judgment based on this amount of data. He is looking forward to a peer-reviewed publication. “I’ll be interested to see what it shows in terms of the details.”
Phase 3 trials of upadacitinib are underway in atopic dermatitis, RA, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, and Takayasu arteritis as well as ulcerative colitis.
In a 52-week maintenance trial, according to a press release, malignancies (excluding nonmelanoma skin cancer) included one event among 148 people taking a 15-mg dose of upadacitinib 15, two events among 154 people taking a 30-mg dose of upadacitinib, and one event among 149 people in the placebo group.
Two cases of pulmonary embolism were reported in the 15-mg group and two cases of deep vein thrombosis were reported in the 30-mg group, compared with one event of ovarian vein thrombosis in the placebo group. One adjudicated major cardiovascular event each were reported in the upadacitinib 30-mg group and the placebo group. No one died.
The study was funded by AbbVie. Dr. Loftus reported that he is a consultant for AbbVie as well as multiple other gastroenterology drug companies. Dr. Eichele disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LAS VEGAS – An oral Janus kinase 1 inhibitor upadacitinib (Rinvoq, AbbVie) showed high efficacy and good safety as a treatment for ulcerative colitis in a phase 3 trial.
The finding could provide some reassurance after the Food and Drug Administration recently warned of an increased risk of cancer and heart disease associated with medications in the same class as upadacitinib.
“Serious adverse events were numerically lower in patients on upadacitinib, and discontinuations from the study due to adverse events were also lower” than in patients taking a placebo, said Edward Loftus, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
Dr. Loftus presented the findings from the U-ACCOMPLISH study at the annual meeting of the American College of Gastroenterology.
Although other medications are approved for the treatment of ulcerative colitis, including biologics, many patients do not respond. In 2019, tofacitinib (Xeljanz) became the first JAK inhibitor approved for this condition. It works by blocking the JAK1 and JAK3 inflammation pathways, and at high concentrations, it also blocks the tyrosine kinase 2 and JAK2 pathways.
However, adverse events seen in clinical trials of tofacitinib include pneumonia, herpes zoster, anal abscess, and Clostridioides difficile infections. And, as reported by this news organization in September, the FDA required its manufacturer, Pfizer, to add a boxed warning that includes information about the risks of stroke, cancer, blood clots, and death.
Upadacitinib may be more selective and reversible because it preferentially blocks JAK1 or JAK1/3. In August 2019, it received FDA approval at a dose of 15 mg for adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate.
But the FDA applied the same warnings to upadacitinib – and to a third related drug, baricitinib (Olumiant) – that it required for tofacitinib, even though they are not as well studied.
The FDA also limited approved uses of these three medications to patients who have not responded well to tumor necrosis factor blockers to ensure their benefits outweigh their risks.
A well-tolerated treatment
U-ACCOMPLISH is one of two phase 3 trials induction trials completed on upadacitinib.
Investigators randomized 522 people with moderately to severely active ulcerative colitis, defined as Adapted Mayo Score 5-9 with a centrally read endoscopic score of 2-3. Of those patients, the intent to treat population included 341 in the upadacitinib group (45 mg once daily) and 174 in the placebo group.
The baseline demographics and disease characteristics were similar between groups. More than two-thirds of patients in both groups were White, and more than two-thirds were men. In the upadacitinib group, 50.7% had responded inadequately to biologic treatments, compared with 51.1% in the placebo group.
After 8 weeks, a significantly higher proportion of patients receiving upadacitinib achieved clinical remission as defined by the adapted Mayo Score (stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ≤1).
“In terms of the efficacy, I think it’s very, very promising,” said Derrick Eichele, MD, an assistant professor of gastroenterology-hepatology at the University of Nebraska Medical Center in Omaha, who was not involved in the trial.
The efficacy data were similar to those reported for tofacitinib in clinical trials, he said in an interview. “But I think again, what we’re waiting to see is how is this going to be positioned in relation to tofacitinib in terms of safety profile.”
More patients in the upadacitinib group reported adverse events, including those deemed related to the drug. However, the proportion that were severe, serious, or led to discontinuation was higher in the placebo group. No one in the study died, and no one in the upadacitinib group had an adjudicated major adverse cardiovascular event, tuberculosis, or malignancy.
The most common adverse events were acne, blood creatine phosphokinase elevation, and anemia, which were all more common in the upadacitinib group, and headache and worsening of ulcerative colitis, which were more common in the placebo group.
Among adverse events of special interest, anemia, neutropenia, hepatic disorder, lymphopenia, serious infection, and opportunistic infection were more common in the upadacitinib group than in the placebo group. The four opportunistic infections in the upadacitinib group included two cases of herpes zoster.
In reviewing the poster presented at this meeting, the cases of neutropenia and hepatic disorder in the upadacitinib group stood out for Dr. Eichele. But he said it’s hard to pass judgment based on this amount of data. He is looking forward to a peer-reviewed publication. “I’ll be interested to see what it shows in terms of the details.”
Phase 3 trials of upadacitinib are underway in atopic dermatitis, RA, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, and Takayasu arteritis as well as ulcerative colitis.
In a 52-week maintenance trial, according to a press release, malignancies (excluding nonmelanoma skin cancer) included one event among 148 people taking a 15-mg dose of upadacitinib 15, two events among 154 people taking a 30-mg dose of upadacitinib, and one event among 149 people in the placebo group.
Two cases of pulmonary embolism were reported in the 15-mg group and two cases of deep vein thrombosis were reported in the 30-mg group, compared with one event of ovarian vein thrombosis in the placebo group. One adjudicated major cardiovascular event each were reported in the upadacitinib 30-mg group and the placebo group. No one died.
The study was funded by AbbVie. Dr. Loftus reported that he is a consultant for AbbVie as well as multiple other gastroenterology drug companies. Dr. Eichele disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACG 2021