Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

A version of this article first appeared on Medscape.com.

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

A version of this article first appeared on Medscape.com.

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved etrasimod (Velsipity, Pfizer) for treating moderate to severe active ulcerative colitis (UC) in adults, Pfizer announced on Oct. 13.

Etrasimod is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. The approved recommended dose is 2 mg once daily.

Etrasimod is the second agent in the S1P class approved for UC in the United States. The other agent, ozanimod (Zeposia, Bristol-Myers Squibb), received FDA approval for moderately to severely active UC in May 2021.

The approval of etrasimod was based on safety and efficacy data from two randomized, double-blind, placebo-controlled phase 3 trials: ELEVATE UC 52 trial and the ELEVATE UC 12 trial. The Lancet published full results from the two trials in March.

Both trials enrolled patients with UC who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase inhibitor therapy.

In ELEVATE UC 52, clinical remission at 12 weeks occurred in 27% of patients taking etrasimod versus 7% of patients taking a placebo (20% difference; P < .001). At week 52, remission rates were 32% with active treatment verus 7% with placebo (26% difference; P < .001).

In ELEVATE UC 12, clinical remission was achieved among 26% of patients who received etrasimod versus 15.0% of patients who received placebo (11% difference; P < .05).

Statistically significant improvements were also observed with etrasimod (vs. placebo) on all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.

The most common side effects of etrasimod were found to be headache, elevated values on liver tests, worsening of UC, SARS-CoV-2 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. Full prescribing information is available online.

Etrasimod is “a proven advanced treatment with a favorable benefit-risk profile,” Michael Chiorean, MD, codirector of the IBD Center at Swedish Medical Center, Seattle, who is an investigator in the ELEVATE studies, said in a Pfizer news release.

“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms. The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of Velsipity for patients across the U.S.,” added Michael Osso, president and CEO of the Crohn’s & Colitis Foundation.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved etrasimod (Velsipity, Pfizer) for treating moderate to severe active ulcerative colitis (UC) in adults, Pfizer announced on Oct. 13.

Etrasimod is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. The approved recommended dose is 2 mg once daily.

Etrasimod is the second agent in the S1P class approved for UC in the United States. The other agent, ozanimod (Zeposia, Bristol-Myers Squibb), received FDA approval for moderately to severely active UC in May 2021.

The approval of etrasimod was based on safety and efficacy data from two randomized, double-blind, placebo-controlled phase 3 trials: ELEVATE UC 52 trial and the ELEVATE UC 12 trial. The Lancet published full results from the two trials in March.

Both trials enrolled patients with UC who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase inhibitor therapy.

In ELEVATE UC 52, clinical remission at 12 weeks occurred in 27% of patients taking etrasimod versus 7% of patients taking a placebo (20% difference; P < .001). At week 52, remission rates were 32% with active treatment verus 7% with placebo (26% difference; P < .001).

In ELEVATE UC 12, clinical remission was achieved among 26% of patients who received etrasimod versus 15.0% of patients who received placebo (11% difference; P < .05).

Statistically significant improvements were also observed with etrasimod (vs. placebo) on all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.

The most common side effects of etrasimod were found to be headache, elevated values on liver tests, worsening of UC, SARS-CoV-2 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. Full prescribing information is available online.

Etrasimod is “a proven advanced treatment with a favorable benefit-risk profile,” Michael Chiorean, MD, codirector of the IBD Center at Swedish Medical Center, Seattle, who is an investigator in the ELEVATE studies, said in a Pfizer news release.

“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms. The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of Velsipity for patients across the U.S.,” added Michael Osso, president and CEO of the Crohn’s & Colitis Foundation.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved etrasimod (Velsipity, Pfizer) for treating moderate to severe active ulcerative colitis (UC) in adults, Pfizer announced on Oct. 13.

Etrasimod is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. The approved recommended dose is 2 mg once daily.

Etrasimod is the second agent in the S1P class approved for UC in the United States. The other agent, ozanimod (Zeposia, Bristol-Myers Squibb), received FDA approval for moderately to severely active UC in May 2021.

The approval of etrasimod was based on safety and efficacy data from two randomized, double-blind, placebo-controlled phase 3 trials: ELEVATE UC 52 trial and the ELEVATE UC 12 trial. The Lancet published full results from the two trials in March.

Both trials enrolled patients with UC who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase inhibitor therapy.

In ELEVATE UC 52, clinical remission at 12 weeks occurred in 27% of patients taking etrasimod versus 7% of patients taking a placebo (20% difference; P < .001). At week 52, remission rates were 32% with active treatment verus 7% with placebo (26% difference; P < .001).

In ELEVATE UC 12, clinical remission was achieved among 26% of patients who received etrasimod versus 15.0% of patients who received placebo (11% difference; P < .05).

Statistically significant improvements were also observed with etrasimod (vs. placebo) on all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.

The most common side effects of etrasimod were found to be headache, elevated values on liver tests, worsening of UC, SARS-CoV-2 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. Full prescribing information is available online.

Etrasimod is “a proven advanced treatment with a favorable benefit-risk profile,” Michael Chiorean, MD, codirector of the IBD Center at Swedish Medical Center, Seattle, who is an investigator in the ELEVATE studies, said in a Pfizer news release.

“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms. The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of Velsipity for patients across the U.S.,” added Michael Osso, president and CEO of the Crohn’s & Colitis Foundation.

A version of this article first appeared on Medscape.com.

In its September meeting, the safety committee (Pharmacovigilance Risk Assessment Committee) of the European Medicines Agency confirmed that atrial fibrillation will now be included as a common side effect in the Summary of Product Characteristics for medicinal products containing omega-3-acid ethyl esters. Should atrial fibrillation develop, intake of the medication must be stopped permanently.

Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.

During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.

The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In its September meeting, the safety committee (Pharmacovigilance Risk Assessment Committee) of the European Medicines Agency confirmed that atrial fibrillation will now be included as a common side effect in the Summary of Product Characteristics for medicinal products containing omega-3-acid ethyl esters. Should atrial fibrillation develop, intake of the medication must be stopped permanently.

Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.

During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.

The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In its September meeting, the safety committee (Pharmacovigilance Risk Assessment Committee) of the European Medicines Agency confirmed that atrial fibrillation will now be included as a common side effect in the Summary of Product Characteristics for medicinal products containing omega-3-acid ethyl esters. Should atrial fibrillation develop, intake of the medication must be stopped permanently.

Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.

During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.

The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

This patient was given a diagnosis of xerosis of the feet, commonly called fissured or cracked heels. Scaling and fissuring are also common in tinea pedis, but the location is often between the toes and there are finer splits and scale.

Xerosis is severely dry skin with hyperkeratosis due to abnormal keratinization;¹ it leads to inflexibility and subsequent fissuring of the heel pads. The cracks can be painful and even bleed.

Although the condition is common, well-controlled trials and definitive evidence in the literature are sparse. The authors of one systematic review were unable to draw conclusions regarding the efficacy of various treatments due to wide variation in research methodologies and outcome measures; they did, however, note that urea-containing products (followed by ammonium lactate products) were studied the most.²

In clinical practice, frequently applied topical emollients are recommended. Exfoliating products, including prescription Lac-Hydrin (ammonium lactate 12% cream) and the over-the-counter version, Am-Lactin, may be helpful. Mechanical debridement with a file or pumice stone can be used (with caution) to reduce the hyperkeratotic plaques. If these measures fail, topical steroids may be added to the emollients. In addition, patients have used cyanoacrylate glues to hold the fissures together with a reported reduction in pain.³

This patient had already tried standard topical emollients. She was prescribed ammonium lactate cream to be used as an exfoliating moisturizer topically twice daily along with triamcinolone acetonide (TAC) 0.1% ointment to be applied twice daily. She was instructed to wean off the TAC once the xerosis was controlled with the ammonium lactate cream.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient was given a diagnosis of xerosis of the feet, commonly called fissured or cracked heels. Scaling and fissuring are also common in tinea pedis, but the location is often between the toes and there are finer splits and scale.

Xerosis is severely dry skin with hyperkeratosis due to abnormal keratinization;¹ it leads to inflexibility and subsequent fissuring of the heel pads. The cracks can be painful and even bleed.

Although the condition is common, well-controlled trials and definitive evidence in the literature are sparse. The authors of one systematic review were unable to draw conclusions regarding the efficacy of various treatments due to wide variation in research methodologies and outcome measures; they did, however, note that urea-containing products (followed by ammonium lactate products) were studied the most.²

In clinical practice, frequently applied topical emollients are recommended. Exfoliating products, including prescription Lac-Hydrin (ammonium lactate 12% cream) and the over-the-counter version, Am-Lactin, may be helpful. Mechanical debridement with a file or pumice stone can be used (with caution) to reduce the hyperkeratotic plaques. If these measures fail, topical steroids may be added to the emollients. In addition, patients have used cyanoacrylate glues to hold the fissures together with a reported reduction in pain.³

This patient had already tried standard topical emollients. She was prescribed ammonium lactate cream to be used as an exfoliating moisturizer topically twice daily along with triamcinolone acetonide (TAC) 0.1% ointment to be applied twice daily. She was instructed to wean off the TAC once the xerosis was controlled with the ammonium lactate cream.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient was given a diagnosis of xerosis of the feet, commonly called fissured or cracked heels. Scaling and fissuring are also common in tinea pedis, but the location is often between the toes and there are finer splits and scale.

Xerosis is severely dry skin with hyperkeratosis due to abnormal keratinization;¹ it leads to inflexibility and subsequent fissuring of the heel pads. The cracks can be painful and even bleed.

Although the condition is common, well-controlled trials and definitive evidence in the literature are sparse. The authors of one systematic review were unable to draw conclusions regarding the efficacy of various treatments due to wide variation in research methodologies and outcome measures; they did, however, note that urea-containing products (followed by ammonium lactate products) were studied the most.²

In clinical practice, frequently applied topical emollients are recommended. Exfoliating products, including prescription Lac-Hydrin (ammonium lactate 12% cream) and the over-the-counter version, Am-Lactin, may be helpful. Mechanical debridement with a file or pumice stone can be used (with caution) to reduce the hyperkeratotic plaques. If these measures fail, topical steroids may be added to the emollients. In addition, patients have used cyanoacrylate glues to hold the fissures together with a reported reduction in pain.³

This patient had already tried standard topical emollients. She was prescribed ammonium lactate cream to be used as an exfoliating moisturizer topically twice daily along with triamcinolone acetonide (TAC) 0.1% ointment to be applied twice daily. She was instructed to wean off the TAC once the xerosis was controlled with the ammonium lactate cream.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

TOPLINE:

High and low levels of HDL cholesterol but not levels of LDL cholesterol are associated with an increased risk for dementia in older adults, a new study found.

METHODOLOGY:

• Electronic health record and survey data on 184,367 Kaiser Permanente Northern California participants (median age, 69.5 years) with no history of dementia were taken.
• Cholesterol levels were measured within 2 years of survey completion.

TAKEAWAY:

• There were 25,214 incident cases of dementia reported over an average follow-up of 8.77 years.
• Dementia risk was significantly higher in people with low HDL cholesterol (11-41 mg/dL; adjusted hazard ratio, 1.07; 95% confidence interval, 1.03-1.11) and high HDL cholesterol (> 65 mg/dL; aHR, 1.15; 95% CI, 1.11-1.20).
• The study demonstrates an association between low and high levels of “good” cholesterol but not a causal link.
• There was no significant association between LDL cholesterol and dementia risk.

IN PRACTICE:

“These results support the conclusion that some lipoproteins may be modifiable risk factors for dementia, even in late life,” the authors wrote.

SOURCE:

The study was conducted by Erin L. Ferguson, MPH, department of epidemiology & biostatistics, University of California, San Francisco, and was funded by the National Institutes of Health. It was published online in Neurology.

LIMITATIONS:

There were no adjustments for apo E status and confounding and selection bias.

DISCLOSURES:

The authors report no relevant disclosures.

A version of this article first appeared on Medscape.com.

TOPLINE:

High and low levels of HDL cholesterol but not levels of LDL cholesterol are associated with an increased risk for dementia in older adults, a new study found.

METHODOLOGY:

• Electronic health record and survey data on 184,367 Kaiser Permanente Northern California participants (median age, 69.5 years) with no history of dementia were taken.
• Cholesterol levels were measured within 2 years of survey completion.

TAKEAWAY:

• There were 25,214 incident cases of dementia reported over an average follow-up of 8.77 years.
• Dementia risk was significantly higher in people with low HDL cholesterol (11-41 mg/dL; adjusted hazard ratio, 1.07; 95% confidence interval, 1.03-1.11) and high HDL cholesterol (> 65 mg/dL; aHR, 1.15; 95% CI, 1.11-1.20).
• The study demonstrates an association between low and high levels of “good” cholesterol but not a causal link.
• There was no significant association between LDL cholesterol and dementia risk.

IN PRACTICE:

“These results support the conclusion that some lipoproteins may be modifiable risk factors for dementia, even in late life,” the authors wrote.

SOURCE:

The study was conducted by Erin L. Ferguson, MPH, department of epidemiology & biostatistics, University of California, San Francisco, and was funded by the National Institutes of Health. It was published online in Neurology.

LIMITATIONS:

There were no adjustments for apo E status and confounding and selection bias.

DISCLOSURES:

The authors report no relevant disclosures.

A version of this article first appeared on Medscape.com.

TOPLINE:

High and low levels of HDL cholesterol but not levels of LDL cholesterol are associated with an increased risk for dementia in older adults, a new study found.

METHODOLOGY:

• Electronic health record and survey data on 184,367 Kaiser Permanente Northern California participants (median age, 69.5 years) with no history of dementia were taken.
• Cholesterol levels were measured within 2 years of survey completion.

TAKEAWAY:

• There were 25,214 incident cases of dementia reported over an average follow-up of 8.77 years.
• Dementia risk was significantly higher in people with low HDL cholesterol (11-41 mg/dL; adjusted hazard ratio, 1.07; 95% confidence interval, 1.03-1.11) and high HDL cholesterol (> 65 mg/dL; aHR, 1.15; 95% CI, 1.11-1.20).
• The study demonstrates an association between low and high levels of “good” cholesterol but not a causal link.
• There was no significant association between LDL cholesterol and dementia risk.

IN PRACTICE:

“These results support the conclusion that some lipoproteins may be modifiable risk factors for dementia, even in late life,” the authors wrote.

SOURCE:

The study was conducted by Erin L. Ferguson, MPH, department of epidemiology & biostatistics, University of California, San Francisco, and was funded by the National Institutes of Health. It was published online in Neurology.

LIMITATIONS:

There were no adjustments for apo E status and confounding and selection bias.

DISCLOSURES:

The authors report no relevant disclosures.

A version of this article first appeared on Medscape.com.

The newly approved respiratory syncytial virus vaccine administered during pregnancy substantially reduces the clinical and economic burden of lower respiratory tract disease caused by RSV, according to research presented at an annual scientific meeting on infectious diseases.

“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.

“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.

This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.

The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
 

Strong efficacy data

Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.

As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
 

New modeling study

Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.

According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.

With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.

Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.

Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.

Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.

Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”

In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.

The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.

A version of this article first appeared on Medscape.com.

The newly approved respiratory syncytial virus vaccine administered during pregnancy substantially reduces the clinical and economic burden of lower respiratory tract disease caused by RSV, according to research presented at an annual scientific meeting on infectious diseases.

“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.

“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.

This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.

The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
 

Strong efficacy data

Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.

As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
 

New modeling study

Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.

According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.

With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.

Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.

Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.

Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.

Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”

In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.

The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.

A version of this article first appeared on Medscape.com.

The newly approved respiratory syncytial virus vaccine administered during pregnancy substantially reduces the clinical and economic burden of lower respiratory tract disease caused by RSV, according to research presented at an annual scientific meeting on infectious diseases.

“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.

“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.

This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.

The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
 

Strong efficacy data

Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.

As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
 

New modeling study

Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.

According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.

With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.

Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.

Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.

Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.

Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”

In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.

The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.

A version of this article first appeared on Medscape.com.

It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.

The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).

The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.

But a secondary analysis identified a subgroup of patients, more than half the total, with a profile of features characterizing them, researchers say, as a group likely to respond favorably to SAVM.

Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.

The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.

The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.

Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
 

How SAVM works

Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.

Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.

The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.

Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”

Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”

Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”

REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.

The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.
 

Predicting SAVM response

In analysis limited to potential responders, PCWP, KCCQ, 6MWD, and natriuretic peptide outcomes for patients were combined into z scores, a single metric that reflects multiple outcomes, Dr. Fudim explained.

The z scores were derived for tertiles of patients in subgroups defined by a range of parameters that included demographics, medical history, and hemodynamic and echocardiographic variables.

Four such variables were found to interact across tertiles in a way that suggested their value as SAVM outcome predictors and were then used to select the cohort of potential responders. The variables were exertion-related changes in cardiac index, pulse pressure, and heart rate, and mitral E/A ratio – the latter a measure of diastolic dysfunction.

Among potential responders, those who underwent SAVM showed a 2.9–mm Hg steeper drop in peak PCWP at 1 month (P = .02), compared with patients getting the sham procedure.

They also bested control patients at both 6 and 12 months for KCCQ score, 6MWD, and natriuretic peptide levels, the latter of which fell in the SAVM group and climbed in control patients at both follow-ups.

“Hypothetically, it makes sense” to target the splanchnic nerve in HFpEF, and indeed in HF with reduced ejection fraction, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

And should SAVM enter the mainstream, it would definitely be important to identify “the right” patients for such an invasive procedure, those likely to show “efficacy with a good safety margin,” said Dr. Bozkurt, who was not associated with REBALANCE-HF.

But the trial, she said, “unfortunately did not give real signals of outcome benefit.”

REBALANCE-HF was supported by Axon Therapies. Dr. Fudim disclosed consulting, receiving royalties, or having ownership or equity in Axon Therapies. Dr. Sharma disclosed receiving honoraria for speaking from Novartis and Janssen and serving on an advisory board or consulting for Novartis, Janssen, and Bayer. Dr. Bozkurt disclosed receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion.

A version of this article first appeared on Medscape.com.

It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.

The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).

The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.

But a secondary analysis identified a subgroup of patients, more than half the total, with a profile of features characterizing them, researchers say, as a group likely to respond favorably to SAVM.

Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.

The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.

The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.

Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
 

How SAVM works

Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.

Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.

The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.

Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”

Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”

Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”

REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.

The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.
 

Predicting SAVM response

In analysis limited to potential responders, PCWP, KCCQ, 6MWD, and natriuretic peptide outcomes for patients were combined into z scores, a single metric that reflects multiple outcomes, Dr. Fudim explained.

The z scores were derived for tertiles of patients in subgroups defined by a range of parameters that included demographics, medical history, and hemodynamic and echocardiographic variables.

Four such variables were found to interact across tertiles in a way that suggested their value as SAVM outcome predictors and were then used to select the cohort of potential responders. The variables were exertion-related changes in cardiac index, pulse pressure, and heart rate, and mitral E/A ratio – the latter a measure of diastolic dysfunction.

Among potential responders, those who underwent SAVM showed a 2.9–mm Hg steeper drop in peak PCWP at 1 month (P = .02), compared with patients getting the sham procedure.

They also bested control patients at both 6 and 12 months for KCCQ score, 6MWD, and natriuretic peptide levels, the latter of which fell in the SAVM group and climbed in control patients at both follow-ups.

“Hypothetically, it makes sense” to target the splanchnic nerve in HFpEF, and indeed in HF with reduced ejection fraction, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

And should SAVM enter the mainstream, it would definitely be important to identify “the right” patients for such an invasive procedure, those likely to show “efficacy with a good safety margin,” said Dr. Bozkurt, who was not associated with REBALANCE-HF.

But the trial, she said, “unfortunately did not give real signals of outcome benefit.”

REBALANCE-HF was supported by Axon Therapies. Dr. Fudim disclosed consulting, receiving royalties, or having ownership or equity in Axon Therapies. Dr. Sharma disclosed receiving honoraria for speaking from Novartis and Janssen and serving on an advisory board or consulting for Novartis, Janssen, and Bayer. Dr. Bozkurt disclosed receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion.

A version of this article first appeared on Medscape.com.

It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.

The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).

The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.

But a secondary analysis identified a subgroup of patients, more than half the total, with a profile of features characterizing them, researchers say, as a group likely to respond favorably to SAVM.

Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.

The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.

The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.

Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
 

How SAVM works

Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.

Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.

The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.

Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”

Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”

Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”

REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.

The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.
 

Predicting SAVM response

In analysis limited to potential responders, PCWP, KCCQ, 6MWD, and natriuretic peptide outcomes for patients were combined into z scores, a single metric that reflects multiple outcomes, Dr. Fudim explained.

The z scores were derived for tertiles of patients in subgroups defined by a range of parameters that included demographics, medical history, and hemodynamic and echocardiographic variables.

Four such variables were found to interact across tertiles in a way that suggested their value as SAVM outcome predictors and were then used to select the cohort of potential responders. The variables were exertion-related changes in cardiac index, pulse pressure, and heart rate, and mitral E/A ratio – the latter a measure of diastolic dysfunction.

Among potential responders, those who underwent SAVM showed a 2.9–mm Hg steeper drop in peak PCWP at 1 month (P = .02), compared with patients getting the sham procedure.

They also bested control patients at both 6 and 12 months for KCCQ score, 6MWD, and natriuretic peptide levels, the latter of which fell in the SAVM group and climbed in control patients at both follow-ups.

“Hypothetically, it makes sense” to target the splanchnic nerve in HFpEF, and indeed in HF with reduced ejection fraction, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

And should SAVM enter the mainstream, it would definitely be important to identify “the right” patients for such an invasive procedure, those likely to show “efficacy with a good safety margin,” said Dr. Bozkurt, who was not associated with REBALANCE-HF.

But the trial, she said, “unfortunately did not give real signals of outcome benefit.”

REBALANCE-HF was supported by Axon Therapies. Dr. Fudim disclosed consulting, receiving royalties, or having ownership or equity in Axon Therapies. Dr. Sharma disclosed receiving honoraria for speaking from Novartis and Janssen and serving on an advisory board or consulting for Novartis, Janssen, and Bayer. Dr. Bozkurt disclosed receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion.

A version of this article first appeared on Medscape.com.

MILAN – Ocrelizumab (Ocrevus) effectively prevents relapse in older patients with multiple sclerosis (MS), researchers have shown for the first time, although the extremely low risk for relapse in this population should be taken into account, they say.

The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.

“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Lack of data in older patients

Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.

“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.

This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”

One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.

To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.

They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.

The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
 

Only relapse rates reduced

With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.

The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.

They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).

The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.

Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).

Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.

He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
 

Muddling the data

Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.

“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.

This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.

The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.

The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.

“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”

Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.

No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.

A version of this article first appeared on Medscape.com.

MILAN – Ocrelizumab (Ocrevus) effectively prevents relapse in older patients with multiple sclerosis (MS), researchers have shown for the first time, although the extremely low risk for relapse in this population should be taken into account, they say.

The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.

“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Lack of data in older patients

Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.

“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.

This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”

One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.

To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.

They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.

The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
 

Only relapse rates reduced

With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.

The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.

They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).

The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.

Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).

Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.

He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
 

Muddling the data

Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.

“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.

This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.

The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.

The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.

“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”

Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.

No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.

A version of this article first appeared on Medscape.com.

MILAN – Ocrelizumab (Ocrevus) effectively prevents relapse in older patients with multiple sclerosis (MS), researchers have shown for the first time, although the extremely low risk for relapse in this population should be taken into account, they say.

The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.

“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Lack of data in older patients

Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.

“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.

This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”

One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.

To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.

They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.

The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
 

Only relapse rates reduced

With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.

The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.

They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).

The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.

Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).

Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.

He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
 

Muddling the data

Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.

“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.

This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.

The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.

The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.

“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”

Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.

No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.

A version of this article first appeared on Medscape.com.

TOPLINE:

An artificial intelligence (AI) model shows potential for detecting early-stage, “hidden” pancreatic cancer on scans of asymptomatic individuals, paving the way for surgical intervention and cure, new research suggests.

METHODOLOGY:

• The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
• Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
• The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.

TAKEAWAY:

• The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
• On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
• Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
• Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
• Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.

IN PRACTICE:

“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”

SOURCE:

Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.

LIMITATIONS:

The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.

DISCLOSURES:

The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

An artificial intelligence (AI) model shows potential for detecting early-stage, “hidden” pancreatic cancer on scans of asymptomatic individuals, paving the way for surgical intervention and cure, new research suggests.

METHODOLOGY:

• The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
• Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
• The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.

TAKEAWAY:

• The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
• On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
• Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
• Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
• Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.

IN PRACTICE:

“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”

SOURCE:

Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.

LIMITATIONS:

The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.

DISCLOSURES:

The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

An artificial intelligence (AI) model shows potential for detecting early-stage, “hidden” pancreatic cancer on scans of asymptomatic individuals, paving the way for surgical intervention and cure, new research suggests.

METHODOLOGY:

• The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
• Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
• The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.

TAKEAWAY:

• The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
• On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
• Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
• Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
• Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.

IN PRACTICE:

“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”

SOURCE:

Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.

LIMITATIONS:

The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.

DISCLOSURES:

The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People taking semaglutide or liraglutide for weight management are at a higher risk for rare but potentially serious gastrointestinal issues, compared with those taking naltrexone/bupropion, according to a large epidemiologic study.

Patients taking either of these glucagonlike peptide-1 (GLP-1) receptor agonists had a 9-fold elevation in risk for pancreatitis. They were also 4 times more likely to develop bowel obstruction and over 3.5 times more likely to experience gastroparesis.

The research letter was published online in JAMA.

Investigators say their findings are not about scaring people off the weight-loss drugs, but instead about increasing awareness that these potential adverse outcomes can happen.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said lead author Mohit Sodhi, MSc, in a news release about the study. Mr. Sodhi is a graduate of the experimental medicine program at the University of British Columbia in Vancouver, and also a 4th-year medical student at UBC.

People taking a GLP-1 agonist to treat diabetes might be more willing to accept the risks, given their potential advantages, especially that of lowering the risk for heart problems, said Mahyar Etminan, PharmD, MSc, the study’s senior author and an expert in drug safety and pharmacoepidemiology at UBC. “But those who are otherwise healthy and just taking them for weight loss might want to be more careful in weighing the risk–benefit equation.”

People taking these drugs for weight loss have an approximately 1%-2% chance of experiencing these events, including a 1% risk for gastroparesis, Dr. Etminan said.
 

Key findings

The study included 4,144 people taking liraglutide, 613 taking semaglutide, and 654 taking naltrexone/bupropion based on medical records between 2006 and 2020.

They included patients with a recent history of obesity but excluded those with diabetes or who had been prescribed another diabetes medication.

The use of GLP-1 agonists, compared with naltrexone/bupropion, was associated with an increased risk for pancreatitis (adjusted hazard ratio, 9.09; 95% confidence interval, 1.25-66.00), bowel obstruction (HR, 4.22; 95% CI, 1.02-17.40), and gastroparesis (HR, 3.67; 95% CI, 1.15-11.90).

The study also found a higher incidence of biliary disease, but the difference was not statistically significant (HR, 1.50; 95% CI, 0.89-2.53). The incidence of biliary disease (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for naltrexone/bupropion.
 

Not the first report of GI issues

“This important paper confirms the safety signals hinted at in previous randomized controlled trials,” said Carel Le Roux, MBChB, PhD, professor of metabolic medicine, Ulster University, Coleraine, Ireland, and professor of experimental pathology at University College Dublin.

“The limitations of the paper are acknowledged but do not detract from the value of the robust data,” Dr. Le Roux said. “Patients should be informed of the low risk of serious complications, such as pancreatitis, gastroparesis, and bowel obstruction, before they start semaglutide or liraglutide.”

This is not the first report of GI issues associated with GLP-1 agonists, but it’s one of the largest. Most reports have been anecdotal. The U.S. Food and Drug Administration announced on Sept. 28 that it would require manufacturers to include a warning about gastrointestinal ileus on the Ozempic (semaglutide) label.

“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” noted Simon Cork, PhD, senior lecturer in physiology, Anglia Ruskin University in Cambridge, England.

Dr. Cork added that “it’s important to look at this in the proper context.” Obesity significantly increases the risk for developing cardiovascular disease, type 2 diabetes, cancer, gallbladder disease, and stroke, risks that fall dramatically with clinically meaningful and sustained weight loss, he said.

“For the overwhelming majority of patients for whom these drugs are targeted (those with the most severe forms of obesity), the benefits of weight loss far outweigh the risks,” Dr. Cork said.

The study was independently supported. Mr. Sodhi, Dr. Etminan, and Dr. Cork report no relevant financial relationships. Dr. Le Roux is a consultant and has received research funding and reimbursement of travel expenses from Novo Nordisk.

A version of this article first appeared on Medscape.com.

People taking semaglutide or liraglutide for weight management are at a higher risk for rare but potentially serious gastrointestinal issues, compared with those taking naltrexone/bupropion, according to a large epidemiologic study.

Patients taking either of these glucagonlike peptide-1 (GLP-1) receptor agonists had a 9-fold elevation in risk for pancreatitis. They were also 4 times more likely to develop bowel obstruction and over 3.5 times more likely to experience gastroparesis.

The research letter was published online in JAMA.

Investigators say their findings are not about scaring people off the weight-loss drugs, but instead about increasing awareness that these potential adverse outcomes can happen.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said lead author Mohit Sodhi, MSc, in a news release about the study. Mr. Sodhi is a graduate of the experimental medicine program at the University of British Columbia in Vancouver, and also a 4th-year medical student at UBC.

People taking a GLP-1 agonist to treat diabetes might be more willing to accept the risks, given their potential advantages, especially that of lowering the risk for heart problems, said Mahyar Etminan, PharmD, MSc, the study’s senior author and an expert in drug safety and pharmacoepidemiology at UBC. “But those who are otherwise healthy and just taking them for weight loss might want to be more careful in weighing the risk–benefit equation.”

People taking these drugs for weight loss have an approximately 1%-2% chance of experiencing these events, including a 1% risk for gastroparesis, Dr. Etminan said.
 

Key findings

The study included 4,144 people taking liraglutide, 613 taking semaglutide, and 654 taking naltrexone/bupropion based on medical records between 2006 and 2020.

They included patients with a recent history of obesity but excluded those with diabetes or who had been prescribed another diabetes medication.

The use of GLP-1 agonists, compared with naltrexone/bupropion, was associated with an increased risk for pancreatitis (adjusted hazard ratio, 9.09; 95% confidence interval, 1.25-66.00), bowel obstruction (HR, 4.22; 95% CI, 1.02-17.40), and gastroparesis (HR, 3.67; 95% CI, 1.15-11.90).

The study also found a higher incidence of biliary disease, but the difference was not statistically significant (HR, 1.50; 95% CI, 0.89-2.53). The incidence of biliary disease (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for naltrexone/bupropion.
 

Not the first report of GI issues

“This important paper confirms the safety signals hinted at in previous randomized controlled trials,” said Carel Le Roux, MBChB, PhD, professor of metabolic medicine, Ulster University, Coleraine, Ireland, and professor of experimental pathology at University College Dublin.

“The limitations of the paper are acknowledged but do not detract from the value of the robust data,” Dr. Le Roux said. “Patients should be informed of the low risk of serious complications, such as pancreatitis, gastroparesis, and bowel obstruction, before they start semaglutide or liraglutide.”

This is not the first report of GI issues associated with GLP-1 agonists, but it’s one of the largest. Most reports have been anecdotal. The U.S. Food and Drug Administration announced on Sept. 28 that it would require manufacturers to include a warning about gastrointestinal ileus on the Ozempic (semaglutide) label.

“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” noted Simon Cork, PhD, senior lecturer in physiology, Anglia Ruskin University in Cambridge, England.

Dr. Cork added that “it’s important to look at this in the proper context.” Obesity significantly increases the risk for developing cardiovascular disease, type 2 diabetes, cancer, gallbladder disease, and stroke, risks that fall dramatically with clinically meaningful and sustained weight loss, he said.

“For the overwhelming majority of patients for whom these drugs are targeted (those with the most severe forms of obesity), the benefits of weight loss far outweigh the risks,” Dr. Cork said.

The study was independently supported. Mr. Sodhi, Dr. Etminan, and Dr. Cork report no relevant financial relationships. Dr. Le Roux is a consultant and has received research funding and reimbursement of travel expenses from Novo Nordisk.

A version of this article first appeared on Medscape.com.

People taking semaglutide or liraglutide for weight management are at a higher risk for rare but potentially serious gastrointestinal issues, compared with those taking naltrexone/bupropion, according to a large epidemiologic study.

Patients taking either of these glucagonlike peptide-1 (GLP-1) receptor agonists had a 9-fold elevation in risk for pancreatitis. They were also 4 times more likely to develop bowel obstruction and over 3.5 times more likely to experience gastroparesis.

The research letter was published online in JAMA.

Investigators say their findings are not about scaring people off the weight-loss drugs, but instead about increasing awareness that these potential adverse outcomes can happen.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said lead author Mohit Sodhi, MSc, in a news release about the study. Mr. Sodhi is a graduate of the experimental medicine program at the University of British Columbia in Vancouver, and also a 4th-year medical student at UBC.

People taking a GLP-1 agonist to treat diabetes might be more willing to accept the risks, given their potential advantages, especially that of lowering the risk for heart problems, said Mahyar Etminan, PharmD, MSc, the study’s senior author and an expert in drug safety and pharmacoepidemiology at UBC. “But those who are otherwise healthy and just taking them for weight loss might want to be more careful in weighing the risk–benefit equation.”

People taking these drugs for weight loss have an approximately 1%-2% chance of experiencing these events, including a 1% risk for gastroparesis, Dr. Etminan said.
 

Key findings

The study included 4,144 people taking liraglutide, 613 taking semaglutide, and 654 taking naltrexone/bupropion based on medical records between 2006 and 2020.

They included patients with a recent history of obesity but excluded those with diabetes or who had been prescribed another diabetes medication.

The use of GLP-1 agonists, compared with naltrexone/bupropion, was associated with an increased risk for pancreatitis (adjusted hazard ratio, 9.09; 95% confidence interval, 1.25-66.00), bowel obstruction (HR, 4.22; 95% CI, 1.02-17.40), and gastroparesis (HR, 3.67; 95% CI, 1.15-11.90).

The study also found a higher incidence of biliary disease, but the difference was not statistically significant (HR, 1.50; 95% CI, 0.89-2.53). The incidence of biliary disease (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for naltrexone/bupropion.
 

Not the first report of GI issues

“This important paper confirms the safety signals hinted at in previous randomized controlled trials,” said Carel Le Roux, MBChB, PhD, professor of metabolic medicine, Ulster University, Coleraine, Ireland, and professor of experimental pathology at University College Dublin.

“The limitations of the paper are acknowledged but do not detract from the value of the robust data,” Dr. Le Roux said. “Patients should be informed of the low risk of serious complications, such as pancreatitis, gastroparesis, and bowel obstruction, before they start semaglutide or liraglutide.”

This is not the first report of GI issues associated with GLP-1 agonists, but it’s one of the largest. Most reports have been anecdotal. The U.S. Food and Drug Administration announced on Sept. 28 that it would require manufacturers to include a warning about gastrointestinal ileus on the Ozempic (semaglutide) label.

“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” noted Simon Cork, PhD, senior lecturer in physiology, Anglia Ruskin University in Cambridge, England.

Dr. Cork added that “it’s important to look at this in the proper context.” Obesity significantly increases the risk for developing cardiovascular disease, type 2 diabetes, cancer, gallbladder disease, and stroke, risks that fall dramatically with clinically meaningful and sustained weight loss, he said.

“For the overwhelming majority of patients for whom these drugs are targeted (those with the most severe forms of obesity), the benefits of weight loss far outweigh the risks,” Dr. Cork said.

The study was independently supported. Mr. Sodhi, Dr. Etminan, and Dr. Cork report no relevant financial relationships. Dr. Le Roux is a consultant and has received research funding and reimbursement of travel expenses from Novo Nordisk.

A version of this article first appeared on Medscape.com.