User login
New research confirms recommendations on COVID-19 boosters in MS
, as currently recommended.
“We have shown that even MS patients whose B cells were depleted from circulation with ocrelizumab can mount immune responses to COVID-19 vaccines,” said lead study author Ilya Kister, MD, of NYU Langone’s Multiple Sclerosis Comprehensive Care Center in New York.
The findings were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
VIOLA study
The data stem from VIOLA, an ongoing prospective study of humoral and cellular immune responses to COVID-19 vaccines in 60 patients with MS receiving ocrelizumab at MS care centers at NYU Langone and the University of Colorado Denver.
The mean age of participants was 38 years, 73% were women, all had been taking ocrelizumab for a mean of 1.7 years, and 45% had had COVID-19 prior to vaccination.
The researchers examined antibody and cellular responses to the two-dose series of mRNA COVID-19 vaccine (80% received the Pfizer-BioNTech vaccine, 18% the Moderna vaccine, and 2% unknown) over 24 weeks. In addition, 57% of the participants received the third dose/booster.
Results showed that antibody and cellular responses to SARS-CoV-2 spike protein significantly increased after the two-dose mRNA COVID-19 vaccination, though antibody responses tended to peak between 4 and 12 weeks and declined thereafter. There was no significant decline in cellular responses at week 24.
“The third dose ‘booster’ again significantly increased antibody and cellular responses compared with the pre–third dose levels,” Dr. Kister said.
“Importantly, cellular responses remained elevated or even increased from 4 weeks to 12 weeks after third dose/booster. Overall, these data strongly support the need for a third dose in MS patients on ocrelizumab,” Dr. Kister added.
Participants with “hybrid immunity” (those who had been infected with SARS-CoV-2 and who had also been vaccinated for COVID) had markedly higher SARS-CoV-2–specific antibody and cellular responses than those of peers with vaccine-only immunity.
CDC recs
Looking ahead, Dr. Kister said the VIOLA investigators plan to present data on the durability of COVID-19 vaccines in ocrelizumab-treated patients up to 48 weeks after the third dose.
For immunocompromised patients, such as those taking ocrelizumab, the Centers for Disease Control and Prevention considers the third dose of mRNA vaccine not as a “booster” but as part of the regular vaccine series.
“In other words, all these patients should receive three doses as part of their ‘primary’ series,” Dr. Kister noted.
The CDC also recommends receiving the updated booster for COVID-19 that became available in September 2022 (the fourth dose of the vaccine).
“Our study did not evaluate the efficacy of this fourth dose; but based on our results, it is reasonable to suppose that the fourth dose would also lead to a further increase in immune defenses,” Dr. Kister said.
The VIOLA study is an investigator-initiated collaboration supported by F. Hoffmann-La Roche Ltd/Genentech Inc. Dr. Kister has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, as currently recommended.
“We have shown that even MS patients whose B cells were depleted from circulation with ocrelizumab can mount immune responses to COVID-19 vaccines,” said lead study author Ilya Kister, MD, of NYU Langone’s Multiple Sclerosis Comprehensive Care Center in New York.
The findings were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
VIOLA study
The data stem from VIOLA, an ongoing prospective study of humoral and cellular immune responses to COVID-19 vaccines in 60 patients with MS receiving ocrelizumab at MS care centers at NYU Langone and the University of Colorado Denver.
The mean age of participants was 38 years, 73% were women, all had been taking ocrelizumab for a mean of 1.7 years, and 45% had had COVID-19 prior to vaccination.
The researchers examined antibody and cellular responses to the two-dose series of mRNA COVID-19 vaccine (80% received the Pfizer-BioNTech vaccine, 18% the Moderna vaccine, and 2% unknown) over 24 weeks. In addition, 57% of the participants received the third dose/booster.
Results showed that antibody and cellular responses to SARS-CoV-2 spike protein significantly increased after the two-dose mRNA COVID-19 vaccination, though antibody responses tended to peak between 4 and 12 weeks and declined thereafter. There was no significant decline in cellular responses at week 24.
“The third dose ‘booster’ again significantly increased antibody and cellular responses compared with the pre–third dose levels,” Dr. Kister said.
“Importantly, cellular responses remained elevated or even increased from 4 weeks to 12 weeks after third dose/booster. Overall, these data strongly support the need for a third dose in MS patients on ocrelizumab,” Dr. Kister added.
Participants with “hybrid immunity” (those who had been infected with SARS-CoV-2 and who had also been vaccinated for COVID) had markedly higher SARS-CoV-2–specific antibody and cellular responses than those of peers with vaccine-only immunity.
CDC recs
Looking ahead, Dr. Kister said the VIOLA investigators plan to present data on the durability of COVID-19 vaccines in ocrelizumab-treated patients up to 48 weeks after the third dose.
For immunocompromised patients, such as those taking ocrelizumab, the Centers for Disease Control and Prevention considers the third dose of mRNA vaccine not as a “booster” but as part of the regular vaccine series.
“In other words, all these patients should receive three doses as part of their ‘primary’ series,” Dr. Kister noted.
The CDC also recommends receiving the updated booster for COVID-19 that became available in September 2022 (the fourth dose of the vaccine).
“Our study did not evaluate the efficacy of this fourth dose; but based on our results, it is reasonable to suppose that the fourth dose would also lead to a further increase in immune defenses,” Dr. Kister said.
The VIOLA study is an investigator-initiated collaboration supported by F. Hoffmann-La Roche Ltd/Genentech Inc. Dr. Kister has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, as currently recommended.
“We have shown that even MS patients whose B cells were depleted from circulation with ocrelizumab can mount immune responses to COVID-19 vaccines,” said lead study author Ilya Kister, MD, of NYU Langone’s Multiple Sclerosis Comprehensive Care Center in New York.
The findings were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
VIOLA study
The data stem from VIOLA, an ongoing prospective study of humoral and cellular immune responses to COVID-19 vaccines in 60 patients with MS receiving ocrelizumab at MS care centers at NYU Langone and the University of Colorado Denver.
The mean age of participants was 38 years, 73% were women, all had been taking ocrelizumab for a mean of 1.7 years, and 45% had had COVID-19 prior to vaccination.
The researchers examined antibody and cellular responses to the two-dose series of mRNA COVID-19 vaccine (80% received the Pfizer-BioNTech vaccine, 18% the Moderna vaccine, and 2% unknown) over 24 weeks. In addition, 57% of the participants received the third dose/booster.
Results showed that antibody and cellular responses to SARS-CoV-2 spike protein significantly increased after the two-dose mRNA COVID-19 vaccination, though antibody responses tended to peak between 4 and 12 weeks and declined thereafter. There was no significant decline in cellular responses at week 24.
“The third dose ‘booster’ again significantly increased antibody and cellular responses compared with the pre–third dose levels,” Dr. Kister said.
“Importantly, cellular responses remained elevated or even increased from 4 weeks to 12 weeks after third dose/booster. Overall, these data strongly support the need for a third dose in MS patients on ocrelizumab,” Dr. Kister added.
Participants with “hybrid immunity” (those who had been infected with SARS-CoV-2 and who had also been vaccinated for COVID) had markedly higher SARS-CoV-2–specific antibody and cellular responses than those of peers with vaccine-only immunity.
CDC recs
Looking ahead, Dr. Kister said the VIOLA investigators plan to present data on the durability of COVID-19 vaccines in ocrelizumab-treated patients up to 48 weeks after the third dose.
For immunocompromised patients, such as those taking ocrelizumab, the Centers for Disease Control and Prevention considers the third dose of mRNA vaccine not as a “booster” but as part of the regular vaccine series.
“In other words, all these patients should receive three doses as part of their ‘primary’ series,” Dr. Kister noted.
The CDC also recommends receiving the updated booster for COVID-19 that became available in September 2022 (the fourth dose of the vaccine).
“Our study did not evaluate the efficacy of this fourth dose; but based on our results, it is reasonable to suppose that the fourth dose would also lead to a further increase in immune defenses,” Dr. Kister said.
The VIOLA study is an investigator-initiated collaboration supported by F. Hoffmann-La Roche Ltd/Genentech Inc. Dr. Kister has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From ECTRIMS 2022
Patients at risk for Barrett’s esophagus rarely screened
Adults with chronic gastroesophageal reflux disease (GERD) are at increased risk for Barrett’s esophagus (BE) – the precursor to esophageal adenocarcinoma (EAC) – but most don’t undergo recommended screening, new research shows.
Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues surveyed 472 adults with chronic GERD who qualify for BE screening and had a recent visit with their primary care provider.
In this diverse population of people at risk for BE and EAC, only 13% had ever been advised to undergo endoscopy to screen for BE and only 5% actually had a prior screening, the study notes.
“These results make it clear that screening is rarely done,” Dr. Kolb told this news organization.
The results of the survey are published online in the American Journal of Gastroenterology.
Concern high, understanding low
Esophageal cancer and BE have increased among middle-aged adults over roughly the past 5 years, and this increase is not because of better or more frequent screening, as reported previously by this news organization.
In fact, the majority of patients who develop EAC do not have a prior diagnosis of BE, which highlights the failure of current BE screening practices, Dr. Kolb and colleagues point out.
Professional gastroenterology society guidelines recommend screening for BE using upper endoscopy for at-risk individuals, which includes those with chronic GERD, along with other risk factors such as age older than 50 years, male sex, white race, smoking, obesity, and family history of BE or EAC.
In the current survey, most individuals said early detection of BE/EAC is important and leads to better outcomes, but most had poor overall knowledge of risk factors and indications for screening.
Only about two-thirds of respondents correctly identified BE risk factors, and only about 20% believed BE screening was necessary with GERD, the researchers note.
Roughly two-thirds of individuals wanted to prioritize BE screening and felt that getting an upper endoscopy would ease their concern.
Yet, 40% had no prior esophagogastroduodenoscopy. These individuals were less knowledgeable about BE/EAC risk and screening recommendations and identified more barriers to completing endoscopy.
“While minorities were most concerned about developing Barrett’s esophagus and cancer, they reported more barriers to screening compared to White participants,” Dr. Kolb said.
Addressing knowledge gaps
The primary care clinician is often the first line for patients with symptomatic acid reflux and the gateway for preventive cancer screening.
Yet, research has shown that primary care clinicians often have trouble identifying who should be screened for BE, and competing clinical issues make it challenging to implement BE screening.
“As gastroenterologists, we must partner with our primary care colleagues to help increase awareness of this lethal disease and improve recognition of risk factors so that eligible patients can be identified and referred for screening,” Dr. Kolb said.
Reached for comment, Seth Gross, MD, clinical chief of the division of gastroenterology and hepatology at New York University Langone Health, said the results “shed light on the fact that patients with GERD don’t have the knowledge of when they should get medical attention and possibly endoscopy.”
“We may need to do a better job of educating our colleagues and patients to know when to seek specialists to potentially get an endoscopy,” Dr. Gross said.
About 90% of esophageal cancers are diagnosed outside of surveillance programs, noted Prasad G. Iyer, MD, a gastroenterologist at Mayo Clinic in Rochester, Minn.
“Patients didn’t even know that they had Barrett’s [esophagus], so they were never under surveillance. They only come to attention after they have trouble with food sticking, and they can’t swallow solid food,” said Dr. Iyer, who wasn’t involved in the survey.
“Unfortunately, there are just so many cancers and so many issues that primary care providers have to deal with that I think this may not be getting the attention it deserves,” he said.
Access to endoscopy is also likely a barrier, Dr. Iyer noted.
“The waiting list may be several months, and I think providers may focus on other things,” he said.
Less-invasive screening options
Fear of endoscopy may be another issue.
In their survey, Dr. Kolb and colleagues found that 20% of respondents reported fear of discomfort with endoscopy as a barrier to completing screening.
But less-invasive screening options are increasingly available or in development.
This includes Cytosponge, a swallowable capsule containing a compressed sponge attached to a string. When withdrawn, the sponge contains esophageal cytology samples that can be used to identify biomarkers for BE.
In a guideline released last spring, the American College of Gastroenterology endorsed Cytosponge as a nonendoscopic BE screening modality, as published in the American Journal of Gastroenterology.
“The strength of the recommendation is conditional, but it’s the first time where [the ACG] is saying that this may be an option for people,” Dr. Gross said.
This research was funded by the American College of Gastroenterology. Dr. Kolb, Dr. Gross, and Dr. Iyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adults with chronic gastroesophageal reflux disease (GERD) are at increased risk for Barrett’s esophagus (BE) – the precursor to esophageal adenocarcinoma (EAC) – but most don’t undergo recommended screening, new research shows.
Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues surveyed 472 adults with chronic GERD who qualify for BE screening and had a recent visit with their primary care provider.
In this diverse population of people at risk for BE and EAC, only 13% had ever been advised to undergo endoscopy to screen for BE and only 5% actually had a prior screening, the study notes.
“These results make it clear that screening is rarely done,” Dr. Kolb told this news organization.
The results of the survey are published online in the American Journal of Gastroenterology.
Concern high, understanding low
Esophageal cancer and BE have increased among middle-aged adults over roughly the past 5 years, and this increase is not because of better or more frequent screening, as reported previously by this news organization.
In fact, the majority of patients who develop EAC do not have a prior diagnosis of BE, which highlights the failure of current BE screening practices, Dr. Kolb and colleagues point out.
Professional gastroenterology society guidelines recommend screening for BE using upper endoscopy for at-risk individuals, which includes those with chronic GERD, along with other risk factors such as age older than 50 years, male sex, white race, smoking, obesity, and family history of BE or EAC.
In the current survey, most individuals said early detection of BE/EAC is important and leads to better outcomes, but most had poor overall knowledge of risk factors and indications for screening.
Only about two-thirds of respondents correctly identified BE risk factors, and only about 20% believed BE screening was necessary with GERD, the researchers note.
Roughly two-thirds of individuals wanted to prioritize BE screening and felt that getting an upper endoscopy would ease their concern.
Yet, 40% had no prior esophagogastroduodenoscopy. These individuals were less knowledgeable about BE/EAC risk and screening recommendations and identified more barriers to completing endoscopy.
“While minorities were most concerned about developing Barrett’s esophagus and cancer, they reported more barriers to screening compared to White participants,” Dr. Kolb said.
Addressing knowledge gaps
The primary care clinician is often the first line for patients with symptomatic acid reflux and the gateway for preventive cancer screening.
Yet, research has shown that primary care clinicians often have trouble identifying who should be screened for BE, and competing clinical issues make it challenging to implement BE screening.
“As gastroenterologists, we must partner with our primary care colleagues to help increase awareness of this lethal disease and improve recognition of risk factors so that eligible patients can be identified and referred for screening,” Dr. Kolb said.
Reached for comment, Seth Gross, MD, clinical chief of the division of gastroenterology and hepatology at New York University Langone Health, said the results “shed light on the fact that patients with GERD don’t have the knowledge of when they should get medical attention and possibly endoscopy.”
“We may need to do a better job of educating our colleagues and patients to know when to seek specialists to potentially get an endoscopy,” Dr. Gross said.
About 90% of esophageal cancers are diagnosed outside of surveillance programs, noted Prasad G. Iyer, MD, a gastroenterologist at Mayo Clinic in Rochester, Minn.
“Patients didn’t even know that they had Barrett’s [esophagus], so they were never under surveillance. They only come to attention after they have trouble with food sticking, and they can’t swallow solid food,” said Dr. Iyer, who wasn’t involved in the survey.
“Unfortunately, there are just so many cancers and so many issues that primary care providers have to deal with that I think this may not be getting the attention it deserves,” he said.
Access to endoscopy is also likely a barrier, Dr. Iyer noted.
“The waiting list may be several months, and I think providers may focus on other things,” he said.
Less-invasive screening options
Fear of endoscopy may be another issue.
In their survey, Dr. Kolb and colleagues found that 20% of respondents reported fear of discomfort with endoscopy as a barrier to completing screening.
But less-invasive screening options are increasingly available or in development.
This includes Cytosponge, a swallowable capsule containing a compressed sponge attached to a string. When withdrawn, the sponge contains esophageal cytology samples that can be used to identify biomarkers for BE.
In a guideline released last spring, the American College of Gastroenterology endorsed Cytosponge as a nonendoscopic BE screening modality, as published in the American Journal of Gastroenterology.
“The strength of the recommendation is conditional, but it’s the first time where [the ACG] is saying that this may be an option for people,” Dr. Gross said.
This research was funded by the American College of Gastroenterology. Dr. Kolb, Dr. Gross, and Dr. Iyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adults with chronic gastroesophageal reflux disease (GERD) are at increased risk for Barrett’s esophagus (BE) – the precursor to esophageal adenocarcinoma (EAC) – but most don’t undergo recommended screening, new research shows.
Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues surveyed 472 adults with chronic GERD who qualify for BE screening and had a recent visit with their primary care provider.
In this diverse population of people at risk for BE and EAC, only 13% had ever been advised to undergo endoscopy to screen for BE and only 5% actually had a prior screening, the study notes.
“These results make it clear that screening is rarely done,” Dr. Kolb told this news organization.
The results of the survey are published online in the American Journal of Gastroenterology.
Concern high, understanding low
Esophageal cancer and BE have increased among middle-aged adults over roughly the past 5 years, and this increase is not because of better or more frequent screening, as reported previously by this news organization.
In fact, the majority of patients who develop EAC do not have a prior diagnosis of BE, which highlights the failure of current BE screening practices, Dr. Kolb and colleagues point out.
Professional gastroenterology society guidelines recommend screening for BE using upper endoscopy for at-risk individuals, which includes those with chronic GERD, along with other risk factors such as age older than 50 years, male sex, white race, smoking, obesity, and family history of BE or EAC.
In the current survey, most individuals said early detection of BE/EAC is important and leads to better outcomes, but most had poor overall knowledge of risk factors and indications for screening.
Only about two-thirds of respondents correctly identified BE risk factors, and only about 20% believed BE screening was necessary with GERD, the researchers note.
Roughly two-thirds of individuals wanted to prioritize BE screening and felt that getting an upper endoscopy would ease their concern.
Yet, 40% had no prior esophagogastroduodenoscopy. These individuals were less knowledgeable about BE/EAC risk and screening recommendations and identified more barriers to completing endoscopy.
“While minorities were most concerned about developing Barrett’s esophagus and cancer, they reported more barriers to screening compared to White participants,” Dr. Kolb said.
Addressing knowledge gaps
The primary care clinician is often the first line for patients with symptomatic acid reflux and the gateway for preventive cancer screening.
Yet, research has shown that primary care clinicians often have trouble identifying who should be screened for BE, and competing clinical issues make it challenging to implement BE screening.
“As gastroenterologists, we must partner with our primary care colleagues to help increase awareness of this lethal disease and improve recognition of risk factors so that eligible patients can be identified and referred for screening,” Dr. Kolb said.
Reached for comment, Seth Gross, MD, clinical chief of the division of gastroenterology and hepatology at New York University Langone Health, said the results “shed light on the fact that patients with GERD don’t have the knowledge of when they should get medical attention and possibly endoscopy.”
“We may need to do a better job of educating our colleagues and patients to know when to seek specialists to potentially get an endoscopy,” Dr. Gross said.
About 90% of esophageal cancers are diagnosed outside of surveillance programs, noted Prasad G. Iyer, MD, a gastroenterologist at Mayo Clinic in Rochester, Minn.
“Patients didn’t even know that they had Barrett’s [esophagus], so they were never under surveillance. They only come to attention after they have trouble with food sticking, and they can’t swallow solid food,” said Dr. Iyer, who wasn’t involved in the survey.
“Unfortunately, there are just so many cancers and so many issues that primary care providers have to deal with that I think this may not be getting the attention it deserves,” he said.
Access to endoscopy is also likely a barrier, Dr. Iyer noted.
“The waiting list may be several months, and I think providers may focus on other things,” he said.
Less-invasive screening options
Fear of endoscopy may be another issue.
In their survey, Dr. Kolb and colleagues found that 20% of respondents reported fear of discomfort with endoscopy as a barrier to completing screening.
But less-invasive screening options are increasingly available or in development.
This includes Cytosponge, a swallowable capsule containing a compressed sponge attached to a string. When withdrawn, the sponge contains esophageal cytology samples that can be used to identify biomarkers for BE.
In a guideline released last spring, the American College of Gastroenterology endorsed Cytosponge as a nonendoscopic BE screening modality, as published in the American Journal of Gastroenterology.
“The strength of the recommendation is conditional, but it’s the first time where [the ACG] is saying that this may be an option for people,” Dr. Gross said.
This research was funded by the American College of Gastroenterology. Dr. Kolb, Dr. Gross, and Dr. Iyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF GASTROENTEROLOGY
FDA rejects bulevirtide for hepatitis D
The U.S. Food and Drug Administration (FDA) has declined to approve bulevirtide, Gilead Sciences’ drug for the treatment of hepatitis delta virus (HDV) infection and compensated liver disease.
In a complete response letter, the FDA voiced concerns over the production and delivery of bulevirtide, an investigational, first-in-class HDV entry-inhibitor that received conditional approved in Europe in 2020.
The FDA did not request new studies to evaluate the safety and efficacy of bulevirtide.
As reported previously by this news organization, data from an ongoing phase 3 trial showed that after 48 weeks of treatment, almost half of those treated with bulevirtide achieved the combined primary endpoint of reduced or undetectable HDV RNA levels and normalized alanine aminotransferase levels.
Chronic HDV infection is the most severe form of viral hepatitis. It is associated with a poor prognosis and high mortality rates.
There are currently no approved treatments for HDV in the United States. Bulevirtide was granted breakthrough therapy and orphan drug designations by the FDA.
Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, wrote in a news release that the company looks forward to “continuing our active discussions with FDA so that we may bring bulevirtide to people living with HDV in the U.S. as soon as possible.”
This is the second manufacturing-related complete response letter Gilead has received in the past 8 months. In March, the FDA rejected the long-acting HIV drug lenacapavir. The drug was sanctioned in Europe and the United Kingdom in September.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration (FDA) has declined to approve bulevirtide, Gilead Sciences’ drug for the treatment of hepatitis delta virus (HDV) infection and compensated liver disease.
In a complete response letter, the FDA voiced concerns over the production and delivery of bulevirtide, an investigational, first-in-class HDV entry-inhibitor that received conditional approved in Europe in 2020.
The FDA did not request new studies to evaluate the safety and efficacy of bulevirtide.
As reported previously by this news organization, data from an ongoing phase 3 trial showed that after 48 weeks of treatment, almost half of those treated with bulevirtide achieved the combined primary endpoint of reduced or undetectable HDV RNA levels and normalized alanine aminotransferase levels.
Chronic HDV infection is the most severe form of viral hepatitis. It is associated with a poor prognosis and high mortality rates.
There are currently no approved treatments for HDV in the United States. Bulevirtide was granted breakthrough therapy and orphan drug designations by the FDA.
Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, wrote in a news release that the company looks forward to “continuing our active discussions with FDA so that we may bring bulevirtide to people living with HDV in the U.S. as soon as possible.”
This is the second manufacturing-related complete response letter Gilead has received in the past 8 months. In March, the FDA rejected the long-acting HIV drug lenacapavir. The drug was sanctioned in Europe and the United Kingdom in September.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration (FDA) has declined to approve bulevirtide, Gilead Sciences’ drug for the treatment of hepatitis delta virus (HDV) infection and compensated liver disease.
In a complete response letter, the FDA voiced concerns over the production and delivery of bulevirtide, an investigational, first-in-class HDV entry-inhibitor that received conditional approved in Europe in 2020.
The FDA did not request new studies to evaluate the safety and efficacy of bulevirtide.
As reported previously by this news organization, data from an ongoing phase 3 trial showed that after 48 weeks of treatment, almost half of those treated with bulevirtide achieved the combined primary endpoint of reduced or undetectable HDV RNA levels and normalized alanine aminotransferase levels.
Chronic HDV infection is the most severe form of viral hepatitis. It is associated with a poor prognosis and high mortality rates.
There are currently no approved treatments for HDV in the United States. Bulevirtide was granted breakthrough therapy and orphan drug designations by the FDA.
Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, wrote in a news release that the company looks forward to “continuing our active discussions with FDA so that we may bring bulevirtide to people living with HDV in the U.S. as soon as possible.”
This is the second manufacturing-related complete response letter Gilead has received in the past 8 months. In March, the FDA rejected the long-acting HIV drug lenacapavir. The drug was sanctioned in Europe and the United Kingdom in September.
A version of this article first appeared on Medscape.com.
‘Unappreciated’ ties between COVID and gut dysbiosis
(BSIs), new research suggests.
“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.
“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”
In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.
Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.
In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.
They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.
This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.
However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.
“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.
Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.
Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.
A version of this article first appeared on Medscape.com.
(BSIs), new research suggests.
“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.
“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”
In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.
Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.
In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.
They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.
This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.
However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.
“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.
Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.
Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.
A version of this article first appeared on Medscape.com.
(BSIs), new research suggests.
“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.
“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”
In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.
Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.
In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.
They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.
This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.
However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.
“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.
Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.
Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
Oral FMT on par with colonic FMT for recurrent C. difficile
A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).
“We present one of the largest cohorts involving people who received capsule FMT. Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.
The study was published online in Clinical Gastroenterology and Hepatology.
The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.
The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.
Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
Effective without procedural risks
To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.
FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.
Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.
The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.
Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.
They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.
Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.
“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.
Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.
One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.
As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
Two good options
The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.
Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.
“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”
However, lack of access to FMT products often is a barrier to treatment, he said.
“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.
Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”
Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.
“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.
Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).
“We present one of the largest cohorts involving people who received capsule FMT. Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.
The study was published online in Clinical Gastroenterology and Hepatology.
The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.
The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.
Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
Effective without procedural risks
To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.
FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.
Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.
The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.
Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.
They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.
Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.
“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.
Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.
One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.
As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
Two good options
The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.
Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.
“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”
However, lack of access to FMT products often is a barrier to treatment, he said.
“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.
Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”
Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.
“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.
Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).
“We present one of the largest cohorts involving people who received capsule FMT. Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.
The study was published online in Clinical Gastroenterology and Hepatology.
The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.
The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.
Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
Effective without procedural risks
To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.
FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.
Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.
The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.
Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.
They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.
Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.
“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.
Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.
One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.
As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
Two good options
The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.
Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.
“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”
However, lack of access to FMT products often is a barrier to treatment, he said.
“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.
Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”
Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.
“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.
Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Is MRI a viable alternative to lumbar puncture for MS diagnosis?
, a new study indicates.
The presence of oligoclonal bands is “very specific for MS and is obtained by lumbar puncture, which is invasive and can be unpleasant, so it is not an ideal test,” said study investigator Daniel Ontaneda, MD, PhD, with the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
In a pilot study, the central vein sign was “highly correlated with the presence of oligoclonal bands and in many cases could serve to prove that a person has MS without the need for a spinal tap,” Dr. Ontaneda said.
The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Reducing the need for lumbar puncture
Oligoclonal bands in cerebrospinal fluid are commonly used as a diagnostic biomarker for MS and can serve to meet the requirement for dissemination in time in the 2017 McDonald criteria. Central vein sign is an emerging neuroimaging biomarker for MS that may improve diagnostic accuracy and reduce the need for lumbar puncture.
For the study, the investigators compared the sensitivity, specificity, and positive predictive value of central vein sign on MRI with that of oligoclonal bands in cerebrospinal fluid for MS diagnosis.
Among the 53 participants, 24 (45%) met 2017 McDonald criteria for dissemination in space and time at baseline, and 27 (51%) met the criteria at 12-month follow-up.
At initial presentation, sensitivity for MS diagnosis was 75% for oligoclonal bands, 83% for central vein sign “Select-3” (3 central vein sign–positive lesions per scan), and 71% for central vein sign “Select-6” (6 central vein sign–positive lesions per scan).
The point estimate of sensitivity of central vein sign was higher than of oligoclonal bands, but there was no significant difference in sensitivities across methods.
Specificity at initial presentation was 76% for oligoclonal bands, 48% for Select-3, and 86% for Select-6.
The presence of oligoclonal bands was more specific than Select-3 for diagnosis of MS at initial presentation (P = .03), as was Select-6 (P = .001). There was no significant difference when comparing cerebrospinal fluid oligoclonal bands with central vein sign Select-6.
At 12-month follow-up, the positive predictive value was 84% for oligoclonal bands and 95% for Select-6; combining oligoclonal bands and Select-6 gave a positive predictive value of 100%.
Dr. Ontaneda said that on the basis of these promising pilot data, the researchers have secured funding from the National Institutes of Health for a prospective study to further investigate the central vein sign as a potential biomarker for MS.
He also said there is “active discussion as to whether central vein sign should be added to the diagnostic criteria for MS.
“We think that it’s probably about time that we have diagnostic biomarkers that are sensitive and specific and can help us do away with complicated criteria to make the diagnosis, in favor of an imaging biomarker,” Dr. Ontaneda said.
A green light for further research
Commenting on the study, Shaheen Lakhan, MD, a neurologist and researcher from Boston, said that, “if an imaging finding on an otherwise routinely done MRI for patients with MS is just as good as analyses from the fluid from a spinal tap, of course, neurologists, and for sure patients, would go for the former.
“However, this study doesn’t fully support that argument just yet. It is retrospective with a tiny sample size, and the full way they standardized assessments and reporting hasn’t been fully reported,” said Dr. Lakhan, who was not involved in the study.
The study does, however, offer a “solid signal to green-light further exploration of a noninvasive assessment that may replace the dreaded spinal tap.
“In general, these principles need to be applied to all our invasive diagnostic criteria from biopsies to risky procedures, and also the incorporation of artificial intelligence/machine learning to aid in standardizing and scaling these assessments – and, frankly, reduce human error in readings,” said Dr. Lakhan.
Funding for the study was provided by the Race to Erase MS Foundation and the NIH. Dr. Ontaneda has received research support from the NIH, the National MS Society, the Patient Centered Outcomes Research Institute, the Race to Erase MS Foundation, Genentech, Sanofi, and Novartis and has consulted for Biogen, Genentech, Sanofi, Janssen, Novartis, and Merck. Dr. Lakhan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study indicates.
The presence of oligoclonal bands is “very specific for MS and is obtained by lumbar puncture, which is invasive and can be unpleasant, so it is not an ideal test,” said study investigator Daniel Ontaneda, MD, PhD, with the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
In a pilot study, the central vein sign was “highly correlated with the presence of oligoclonal bands and in many cases could serve to prove that a person has MS without the need for a spinal tap,” Dr. Ontaneda said.
The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Reducing the need for lumbar puncture
Oligoclonal bands in cerebrospinal fluid are commonly used as a diagnostic biomarker for MS and can serve to meet the requirement for dissemination in time in the 2017 McDonald criteria. Central vein sign is an emerging neuroimaging biomarker for MS that may improve diagnostic accuracy and reduce the need for lumbar puncture.
For the study, the investigators compared the sensitivity, specificity, and positive predictive value of central vein sign on MRI with that of oligoclonal bands in cerebrospinal fluid for MS diagnosis.
Among the 53 participants, 24 (45%) met 2017 McDonald criteria for dissemination in space and time at baseline, and 27 (51%) met the criteria at 12-month follow-up.
At initial presentation, sensitivity for MS diagnosis was 75% for oligoclonal bands, 83% for central vein sign “Select-3” (3 central vein sign–positive lesions per scan), and 71% for central vein sign “Select-6” (6 central vein sign–positive lesions per scan).
The point estimate of sensitivity of central vein sign was higher than of oligoclonal bands, but there was no significant difference in sensitivities across methods.
Specificity at initial presentation was 76% for oligoclonal bands, 48% for Select-3, and 86% for Select-6.
The presence of oligoclonal bands was more specific than Select-3 for diagnosis of MS at initial presentation (P = .03), as was Select-6 (P = .001). There was no significant difference when comparing cerebrospinal fluid oligoclonal bands with central vein sign Select-6.
At 12-month follow-up, the positive predictive value was 84% for oligoclonal bands and 95% for Select-6; combining oligoclonal bands and Select-6 gave a positive predictive value of 100%.
Dr. Ontaneda said that on the basis of these promising pilot data, the researchers have secured funding from the National Institutes of Health for a prospective study to further investigate the central vein sign as a potential biomarker for MS.
He also said there is “active discussion as to whether central vein sign should be added to the diagnostic criteria for MS.
“We think that it’s probably about time that we have diagnostic biomarkers that are sensitive and specific and can help us do away with complicated criteria to make the diagnosis, in favor of an imaging biomarker,” Dr. Ontaneda said.
A green light for further research
Commenting on the study, Shaheen Lakhan, MD, a neurologist and researcher from Boston, said that, “if an imaging finding on an otherwise routinely done MRI for patients with MS is just as good as analyses from the fluid from a spinal tap, of course, neurologists, and for sure patients, would go for the former.
“However, this study doesn’t fully support that argument just yet. It is retrospective with a tiny sample size, and the full way they standardized assessments and reporting hasn’t been fully reported,” said Dr. Lakhan, who was not involved in the study.
The study does, however, offer a “solid signal to green-light further exploration of a noninvasive assessment that may replace the dreaded spinal tap.
“In general, these principles need to be applied to all our invasive diagnostic criteria from biopsies to risky procedures, and also the incorporation of artificial intelligence/machine learning to aid in standardizing and scaling these assessments – and, frankly, reduce human error in readings,” said Dr. Lakhan.
Funding for the study was provided by the Race to Erase MS Foundation and the NIH. Dr. Ontaneda has received research support from the NIH, the National MS Society, the Patient Centered Outcomes Research Institute, the Race to Erase MS Foundation, Genentech, Sanofi, and Novartis and has consulted for Biogen, Genentech, Sanofi, Janssen, Novartis, and Merck. Dr. Lakhan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study indicates.
The presence of oligoclonal bands is “very specific for MS and is obtained by lumbar puncture, which is invasive and can be unpleasant, so it is not an ideal test,” said study investigator Daniel Ontaneda, MD, PhD, with the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
In a pilot study, the central vein sign was “highly correlated with the presence of oligoclonal bands and in many cases could serve to prove that a person has MS without the need for a spinal tap,” Dr. Ontaneda said.
The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Reducing the need for lumbar puncture
Oligoclonal bands in cerebrospinal fluid are commonly used as a diagnostic biomarker for MS and can serve to meet the requirement for dissemination in time in the 2017 McDonald criteria. Central vein sign is an emerging neuroimaging biomarker for MS that may improve diagnostic accuracy and reduce the need for lumbar puncture.
For the study, the investigators compared the sensitivity, specificity, and positive predictive value of central vein sign on MRI with that of oligoclonal bands in cerebrospinal fluid for MS diagnosis.
Among the 53 participants, 24 (45%) met 2017 McDonald criteria for dissemination in space and time at baseline, and 27 (51%) met the criteria at 12-month follow-up.
At initial presentation, sensitivity for MS diagnosis was 75% for oligoclonal bands, 83% for central vein sign “Select-3” (3 central vein sign–positive lesions per scan), and 71% for central vein sign “Select-6” (6 central vein sign–positive lesions per scan).
The point estimate of sensitivity of central vein sign was higher than of oligoclonal bands, but there was no significant difference in sensitivities across methods.
Specificity at initial presentation was 76% for oligoclonal bands, 48% for Select-3, and 86% for Select-6.
The presence of oligoclonal bands was more specific than Select-3 for diagnosis of MS at initial presentation (P = .03), as was Select-6 (P = .001). There was no significant difference when comparing cerebrospinal fluid oligoclonal bands with central vein sign Select-6.
At 12-month follow-up, the positive predictive value was 84% for oligoclonal bands and 95% for Select-6; combining oligoclonal bands and Select-6 gave a positive predictive value of 100%.
Dr. Ontaneda said that on the basis of these promising pilot data, the researchers have secured funding from the National Institutes of Health for a prospective study to further investigate the central vein sign as a potential biomarker for MS.
He also said there is “active discussion as to whether central vein sign should be added to the diagnostic criteria for MS.
“We think that it’s probably about time that we have diagnostic biomarkers that are sensitive and specific and can help us do away with complicated criteria to make the diagnosis, in favor of an imaging biomarker,” Dr. Ontaneda said.
A green light for further research
Commenting on the study, Shaheen Lakhan, MD, a neurologist and researcher from Boston, said that, “if an imaging finding on an otherwise routinely done MRI for patients with MS is just as good as analyses from the fluid from a spinal tap, of course, neurologists, and for sure patients, would go for the former.
“However, this study doesn’t fully support that argument just yet. It is retrospective with a tiny sample size, and the full way they standardized assessments and reporting hasn’t been fully reported,” said Dr. Lakhan, who was not involved in the study.
The study does, however, offer a “solid signal to green-light further exploration of a noninvasive assessment that may replace the dreaded spinal tap.
“In general, these principles need to be applied to all our invasive diagnostic criteria from biopsies to risky procedures, and also the incorporation of artificial intelligence/machine learning to aid in standardizing and scaling these assessments – and, frankly, reduce human error in readings,” said Dr. Lakhan.
Funding for the study was provided by the Race to Erase MS Foundation and the NIH. Dr. Ontaneda has received research support from the NIH, the National MS Society, the Patient Centered Outcomes Research Institute, the Race to Erase MS Foundation, Genentech, Sanofi, and Novartis and has consulted for Biogen, Genentech, Sanofi, Janssen, Novartis, and Merck. Dr. Lakhan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2022
A better way to predict fall risk in patients with MS?
Compared with patients with MS who didn’t fall, those who did fall had worse neuromuscular function as evidenced by a reduced rate of force development.
“Our study suggests that instead of looking at reduced maximum muscle strength, perhaps we should start looking at reduced rate of force development when trying to identify potential fallers,” said Laurits Taul-Madsen, PhD student, Aarhus University, Denmark.
The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Explosive strength
In contrast to maximal muscle strength, the rate of force development is a measure of explosive strength, or simply the amount of force that an individual can produce over a given time period. When a patient is about to fall, what’s most important is not how strong the person is, but how quickly they can produce enough force to counteract the balance perturbation, thus avoid falling, said Dr. Taul-Madsen.
“If a person is very slow to produce this force, [that person] will have fallen before he or she has produced enough force to counteract the balance perturbation that the person is experiencing,” he added.
Research has shown a reduced rate of force development (RFD) in patients with MS, compared with healthy controls. However, little is known about the impact of RFD on falls in those with MS.
To investigate, researchers studied 53 adults with MS: Twenty-four had no fall history in the prior year, 16 had one to two prior falls, and 13 had three or more falls. The two groups of fallers were both slightly older and had a slightly higher Expanded Disability Status Scale (EDSS) scores, “which may not be so surprising,” Dr. Taul-Madsen said.
Knee extensor neuromuscular function, including maximum muscle strength and RFD at 50 and 200 milliseconds, was assessed via isokinetic dynamometry.
A high RFD is “good and the non-fallers had the highest RFD at 50 ms.” On this measure, “we saw quite a big difference between the non-fallers and the two groups of fallers,” Dr. Taul-Madsen reported.
At 200 ms, the RFD was again highest in the group of non-fallers but the difference was somewhat smaller. Non-fallers also had greater maximum muscle strength than that of the fallers.
There was “good” correlation between these neuromuscular measurements and falls, Dr. Taul-Madsen said.
He noted that RFD, which can be improved with resistance training, “seems like a specialized and difficult measurement, but it doesn’t have to be. It can be measured with just a linear encoder and a chair to perform the sit-to-stand test, so in clinical practice, it’s quite easily measured.”
‘Highly promising’ approach
“There are some data on predictors of falls in persons with MS, but not yet on neuromuscular function, as has been done in other populations,” said Brian Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J.
This study is “interesting in that recurrent fallers were distinguished based on having worse neuromuscular function,” said Dr. Sandroff, who was not part of the research team.
“Although this relationship is somewhat intuitive,” RFD provides a “potentially sensitive measure that can be addressed via specific resistance exercise programs as a highly promising approach for reducing fall risk and falls themselves in persons with MS,” Dr. Sandroff said.
More generally, he said this study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS.
“The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.
The study had no specific funding. Dr. Taul-Madsen and Dr. Sandroff report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Compared with patients with MS who didn’t fall, those who did fall had worse neuromuscular function as evidenced by a reduced rate of force development.
“Our study suggests that instead of looking at reduced maximum muscle strength, perhaps we should start looking at reduced rate of force development when trying to identify potential fallers,” said Laurits Taul-Madsen, PhD student, Aarhus University, Denmark.
The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Explosive strength
In contrast to maximal muscle strength, the rate of force development is a measure of explosive strength, or simply the amount of force that an individual can produce over a given time period. When a patient is about to fall, what’s most important is not how strong the person is, but how quickly they can produce enough force to counteract the balance perturbation, thus avoid falling, said Dr. Taul-Madsen.
“If a person is very slow to produce this force, [that person] will have fallen before he or she has produced enough force to counteract the balance perturbation that the person is experiencing,” he added.
Research has shown a reduced rate of force development (RFD) in patients with MS, compared with healthy controls. However, little is known about the impact of RFD on falls in those with MS.
To investigate, researchers studied 53 adults with MS: Twenty-four had no fall history in the prior year, 16 had one to two prior falls, and 13 had three or more falls. The two groups of fallers were both slightly older and had a slightly higher Expanded Disability Status Scale (EDSS) scores, “which may not be so surprising,” Dr. Taul-Madsen said.
Knee extensor neuromuscular function, including maximum muscle strength and RFD at 50 and 200 milliseconds, was assessed via isokinetic dynamometry.
A high RFD is “good and the non-fallers had the highest RFD at 50 ms.” On this measure, “we saw quite a big difference between the non-fallers and the two groups of fallers,” Dr. Taul-Madsen reported.
At 200 ms, the RFD was again highest in the group of non-fallers but the difference was somewhat smaller. Non-fallers also had greater maximum muscle strength than that of the fallers.
There was “good” correlation between these neuromuscular measurements and falls, Dr. Taul-Madsen said.
He noted that RFD, which can be improved with resistance training, “seems like a specialized and difficult measurement, but it doesn’t have to be. It can be measured with just a linear encoder and a chair to perform the sit-to-stand test, so in clinical practice, it’s quite easily measured.”
‘Highly promising’ approach
“There are some data on predictors of falls in persons with MS, but not yet on neuromuscular function, as has been done in other populations,” said Brian Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J.
This study is “interesting in that recurrent fallers were distinguished based on having worse neuromuscular function,” said Dr. Sandroff, who was not part of the research team.
“Although this relationship is somewhat intuitive,” RFD provides a “potentially sensitive measure that can be addressed via specific resistance exercise programs as a highly promising approach for reducing fall risk and falls themselves in persons with MS,” Dr. Sandroff said.
More generally, he said this study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS.
“The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.
The study had no specific funding. Dr. Taul-Madsen and Dr. Sandroff report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Compared with patients with MS who didn’t fall, those who did fall had worse neuromuscular function as evidenced by a reduced rate of force development.
“Our study suggests that instead of looking at reduced maximum muscle strength, perhaps we should start looking at reduced rate of force development when trying to identify potential fallers,” said Laurits Taul-Madsen, PhD student, Aarhus University, Denmark.
The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Explosive strength
In contrast to maximal muscle strength, the rate of force development is a measure of explosive strength, or simply the amount of force that an individual can produce over a given time period. When a patient is about to fall, what’s most important is not how strong the person is, but how quickly they can produce enough force to counteract the balance perturbation, thus avoid falling, said Dr. Taul-Madsen.
“If a person is very slow to produce this force, [that person] will have fallen before he or she has produced enough force to counteract the balance perturbation that the person is experiencing,” he added.
Research has shown a reduced rate of force development (RFD) in patients with MS, compared with healthy controls. However, little is known about the impact of RFD on falls in those with MS.
To investigate, researchers studied 53 adults with MS: Twenty-four had no fall history in the prior year, 16 had one to two prior falls, and 13 had three or more falls. The two groups of fallers were both slightly older and had a slightly higher Expanded Disability Status Scale (EDSS) scores, “which may not be so surprising,” Dr. Taul-Madsen said.
Knee extensor neuromuscular function, including maximum muscle strength and RFD at 50 and 200 milliseconds, was assessed via isokinetic dynamometry.
A high RFD is “good and the non-fallers had the highest RFD at 50 ms.” On this measure, “we saw quite a big difference between the non-fallers and the two groups of fallers,” Dr. Taul-Madsen reported.
At 200 ms, the RFD was again highest in the group of non-fallers but the difference was somewhat smaller. Non-fallers also had greater maximum muscle strength than that of the fallers.
There was “good” correlation between these neuromuscular measurements and falls, Dr. Taul-Madsen said.
He noted that RFD, which can be improved with resistance training, “seems like a specialized and difficult measurement, but it doesn’t have to be. It can be measured with just a linear encoder and a chair to perform the sit-to-stand test, so in clinical practice, it’s quite easily measured.”
‘Highly promising’ approach
“There are some data on predictors of falls in persons with MS, but not yet on neuromuscular function, as has been done in other populations,” said Brian Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J.
This study is “interesting in that recurrent fallers were distinguished based on having worse neuromuscular function,” said Dr. Sandroff, who was not part of the research team.
“Although this relationship is somewhat intuitive,” RFD provides a “potentially sensitive measure that can be addressed via specific resistance exercise programs as a highly promising approach for reducing fall risk and falls themselves in persons with MS,” Dr. Sandroff said.
More generally, he said this study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS.
“The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.
The study had no specific funding. Dr. Taul-Madsen and Dr. Sandroff report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2022
Higher cardiovascular fitness may help preserve mobility in MS
Investigators found that over time, lower cardiorespiratory fitness predicts increased variability in stride time and could represent a biomarker for subtle neuromuscular decline in patients with MS.
Cardiorespiratory fitness “may exert neuroprotective effects on the central nervous system,” study investigator Syamala Buragadda, neurophysical therapist and PhD candidate, Memorial University, St. John’s, Nfld..
She reported her research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Gait changes
Gait is a complicated process involving coordination of multiple systems, but steps are almost always consistent and symmetric, said Ms. Buragadda. Patients with MS can experience subtle declines in gait quality even without relapses. Considering the neuroprotective properties of exercise, having higher fitness levels could prevent brain atrophy and protect against subtle gait changes.
Calculating stride time variability is a sensitive method to map changes in gait quality.
Ms. Buragadda, with co-investigator Michelle Ploughman, PhD, also with Memorial University, evaluated stride time variability over time in people with MS and explored whether cardiorespiratory fitness predicts stride time variability.
They recruited 49 adults with relapsing-remitting MS (63% women) and mild disability (Expanded Disability Status Scale [EDSS] score < 4; median, 2.0) from MS clinics in Canada. None required walking aids, and none had experienced relapses in the prior 3 months.
Gait quality was assessed on an instrumented walkway, and variability was measured as the coefficient of variation of stride time. Cardiorespiratory fitness was measured as maximal oxygen uptake (VO2max) during a graded exercise test using recumbent stepper. Tests were conducted 2 years apart.
There were no significant changes in EDSS scores over the study period. However, stride time variability increased from 7.3% at baseline to 8.3% at 2 years.
Cardiorespiratory fitness at baseline significantly correlated with stride time variability 2 years later (P = .016) and was a significant predictor of stride time variability at 2 years, accounting for 10% of its variance, Ms. Buragadda reported.
Stride time variability, measured on an instrumented walkway, could be a biomarker for subtle changes to walking and balance, she said.
Limitations of the study include a convenience sample that may not represent the diversity of MS. Also, assessments were made at only two time points, and more time points would likely yield better predictive power. In addition, the lack of MRI images limits correlating structural changes with clinical observations of gait changes.
A buffer against disability?
In a comment, Valerie Block, physical therapist and adjunct instructor, department of physical therapy and rehabilitation science, University of California, San Francisco, and UCSF Weill Institute for Neuroscience, said the findings in this study are not surprising and align with what she has observed, subjectively, in her work.
“In the general population, cardiovascular fitness has a wide array of benefits. Depending on what means the person uses to maintain or improve cardiovascular fitness (that is, running, walking, swimming, etc.), this would have the potential for neuroplastic effects on gait – even in MS and other neurological disorders,” Ms. Block said.
Also offering perspective, Brain Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J., said the study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS. The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.
He noted that the findings from this study coincide with some other data that showed that premorbid physical activity is associated with reduced mobility decline over time in persons with MS.
“Collectively, the data suggest that perhaps engaging in exercise training early in the disease (or having better cardiorespiratory fitness at diagnosis) provides a buffer against disability progression over time,” Dr. Sandroff said.
He said it would be interesting to see whether “physical fitness/premorbid physical activity provides such a buffer in those who already demonstrate mobility problems.”
The study had no specific funding. Ms. Buragadda, Dr. Ploughman, Ms. Block, and Dr. Sandroff have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators found that over time, lower cardiorespiratory fitness predicts increased variability in stride time and could represent a biomarker for subtle neuromuscular decline in patients with MS.
Cardiorespiratory fitness “may exert neuroprotective effects on the central nervous system,” study investigator Syamala Buragadda, neurophysical therapist and PhD candidate, Memorial University, St. John’s, Nfld..
She reported her research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Gait changes
Gait is a complicated process involving coordination of multiple systems, but steps are almost always consistent and symmetric, said Ms. Buragadda. Patients with MS can experience subtle declines in gait quality even without relapses. Considering the neuroprotective properties of exercise, having higher fitness levels could prevent brain atrophy and protect against subtle gait changes.
Calculating stride time variability is a sensitive method to map changes in gait quality.
Ms. Buragadda, with co-investigator Michelle Ploughman, PhD, also with Memorial University, evaluated stride time variability over time in people with MS and explored whether cardiorespiratory fitness predicts stride time variability.
They recruited 49 adults with relapsing-remitting MS (63% women) and mild disability (Expanded Disability Status Scale [EDSS] score < 4; median, 2.0) from MS clinics in Canada. None required walking aids, and none had experienced relapses in the prior 3 months.
Gait quality was assessed on an instrumented walkway, and variability was measured as the coefficient of variation of stride time. Cardiorespiratory fitness was measured as maximal oxygen uptake (VO2max) during a graded exercise test using recumbent stepper. Tests were conducted 2 years apart.
There were no significant changes in EDSS scores over the study period. However, stride time variability increased from 7.3% at baseline to 8.3% at 2 years.
Cardiorespiratory fitness at baseline significantly correlated with stride time variability 2 years later (P = .016) and was a significant predictor of stride time variability at 2 years, accounting for 10% of its variance, Ms. Buragadda reported.
Stride time variability, measured on an instrumented walkway, could be a biomarker for subtle changes to walking and balance, she said.
Limitations of the study include a convenience sample that may not represent the diversity of MS. Also, assessments were made at only two time points, and more time points would likely yield better predictive power. In addition, the lack of MRI images limits correlating structural changes with clinical observations of gait changes.
A buffer against disability?
In a comment, Valerie Block, physical therapist and adjunct instructor, department of physical therapy and rehabilitation science, University of California, San Francisco, and UCSF Weill Institute for Neuroscience, said the findings in this study are not surprising and align with what she has observed, subjectively, in her work.
“In the general population, cardiovascular fitness has a wide array of benefits. Depending on what means the person uses to maintain or improve cardiovascular fitness (that is, running, walking, swimming, etc.), this would have the potential for neuroplastic effects on gait – even in MS and other neurological disorders,” Ms. Block said.
Also offering perspective, Brain Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J., said the study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS. The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.
He noted that the findings from this study coincide with some other data that showed that premorbid physical activity is associated with reduced mobility decline over time in persons with MS.
“Collectively, the data suggest that perhaps engaging in exercise training early in the disease (or having better cardiorespiratory fitness at diagnosis) provides a buffer against disability progression over time,” Dr. Sandroff said.
He said it would be interesting to see whether “physical fitness/premorbid physical activity provides such a buffer in those who already demonstrate mobility problems.”
The study had no specific funding. Ms. Buragadda, Dr. Ploughman, Ms. Block, and Dr. Sandroff have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators found that over time, lower cardiorespiratory fitness predicts increased variability in stride time and could represent a biomarker for subtle neuromuscular decline in patients with MS.
Cardiorespiratory fitness “may exert neuroprotective effects on the central nervous system,” study investigator Syamala Buragadda, neurophysical therapist and PhD candidate, Memorial University, St. John’s, Nfld..
She reported her research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Gait changes
Gait is a complicated process involving coordination of multiple systems, but steps are almost always consistent and symmetric, said Ms. Buragadda. Patients with MS can experience subtle declines in gait quality even without relapses. Considering the neuroprotective properties of exercise, having higher fitness levels could prevent brain atrophy and protect against subtle gait changes.
Calculating stride time variability is a sensitive method to map changes in gait quality.
Ms. Buragadda, with co-investigator Michelle Ploughman, PhD, also with Memorial University, evaluated stride time variability over time in people with MS and explored whether cardiorespiratory fitness predicts stride time variability.
They recruited 49 adults with relapsing-remitting MS (63% women) and mild disability (Expanded Disability Status Scale [EDSS] score < 4; median, 2.0) from MS clinics in Canada. None required walking aids, and none had experienced relapses in the prior 3 months.
Gait quality was assessed on an instrumented walkway, and variability was measured as the coefficient of variation of stride time. Cardiorespiratory fitness was measured as maximal oxygen uptake (VO2max) during a graded exercise test using recumbent stepper. Tests were conducted 2 years apart.
There were no significant changes in EDSS scores over the study period. However, stride time variability increased from 7.3% at baseline to 8.3% at 2 years.
Cardiorespiratory fitness at baseline significantly correlated with stride time variability 2 years later (P = .016) and was a significant predictor of stride time variability at 2 years, accounting for 10% of its variance, Ms. Buragadda reported.
Stride time variability, measured on an instrumented walkway, could be a biomarker for subtle changes to walking and balance, she said.
Limitations of the study include a convenience sample that may not represent the diversity of MS. Also, assessments were made at only two time points, and more time points would likely yield better predictive power. In addition, the lack of MRI images limits correlating structural changes with clinical observations of gait changes.
A buffer against disability?
In a comment, Valerie Block, physical therapist and adjunct instructor, department of physical therapy and rehabilitation science, University of California, San Francisco, and UCSF Weill Institute for Neuroscience, said the findings in this study are not surprising and align with what she has observed, subjectively, in her work.
“In the general population, cardiovascular fitness has a wide array of benefits. Depending on what means the person uses to maintain or improve cardiovascular fitness (that is, running, walking, swimming, etc.), this would have the potential for neuroplastic effects on gait – even in MS and other neurological disorders,” Ms. Block said.
Also offering perspective, Brain Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J., said the study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS. The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.
He noted that the findings from this study coincide with some other data that showed that premorbid physical activity is associated with reduced mobility decline over time in persons with MS.
“Collectively, the data suggest that perhaps engaging in exercise training early in the disease (or having better cardiorespiratory fitness at diagnosis) provides a buffer against disability progression over time,” Dr. Sandroff said.
He said it would be interesting to see whether “physical fitness/premorbid physical activity provides such a buffer in those who already demonstrate mobility problems.”
The study had no specific funding. Ms. Buragadda, Dr. Ploughman, Ms. Block, and Dr. Sandroff have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2022
Two biologics equally effective for extraintestinal manifestations of IBD
Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.
Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.
Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.
Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.
To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).
After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.
After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.
Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.
A similar pattern emerged when looking at improvement in EIM.
At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).
At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).
Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.
Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”
Limitations of the study include its retrospective design and small cohort size.
Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.
Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.
Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.
Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.
The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.
A version of this article first appeared on Medscape.com.
Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.
Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.
Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.
Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.
To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).
After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.
After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.
Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.
A similar pattern emerged when looking at improvement in EIM.
At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).
At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).
Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.
Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”
Limitations of the study include its retrospective design and small cohort size.
Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.
Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.
Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.
Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.
The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.
A version of this article first appeared on Medscape.com.
Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.
Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.
Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.
Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.
To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).
After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.
After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.
Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.
A similar pattern emerged when looking at improvement in EIM.
At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).
At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).
Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.
Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”
Limitations of the study include its retrospective design and small cohort size.
Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.
Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.
Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.
Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.
The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.
A version of this article first appeared on Medscape.com.
FROM DIGESTIVE AND LIVER DISEASE
Time to ditch clarithromycin for H. pylori?
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.