Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.

In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.

“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.

“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.

“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing bleed rates

Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.

Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.

Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.

In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.

Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.

Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.

Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.

“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.

Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.

“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
 

Considering future research

In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.

“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.

Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.

In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.

“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”

Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.

“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”

The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.

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

Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.

In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.

“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.

“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.

“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing bleed rates

Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.

Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.

Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.

In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.

Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.

Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.

Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.

“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.

Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.

“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
 

Considering future research

In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.

“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.

Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.

In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.

“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”

Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.

“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”

The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.

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

Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.

In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.

“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.

“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.

“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing bleed rates

Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.

Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.

Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.

In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.

Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.

Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.

Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.

“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.

Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.

“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
 

Considering future research

In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.

“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.

Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.

In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.

“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”

Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.

“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”

The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.

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

A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.

Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.

“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.

“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.

The study was published online in the American Journal of Gastroenterology.
 

Taking a second look

Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.

To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.

First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.

However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).

The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.

The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.

While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.

They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
 

Good study, reassuring data

“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”

Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.

“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.

“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.

NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.

In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”

Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.

“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.

The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.

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

A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.

Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.

“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.

“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.

The study was published online in the American Journal of Gastroenterology.
 

Taking a second look

Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.

To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.

First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.

However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).

The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.

The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.

While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.

They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
 

Good study, reassuring data

“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”

Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.

“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.

“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.

NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.

In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”

Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.

“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.

The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.

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

A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.

Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.

“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.

“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.

The study was published online in the American Journal of Gastroenterology.
 

Taking a second look

Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.

To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.

First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.

However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).

The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.

The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.

While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.

They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
 

Good study, reassuring data

“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”

Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.

“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.

“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.

NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.

In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”

Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.

“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.

The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.

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

It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.

This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.

“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.

“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.

The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations

The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.

The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.

“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.

Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.

“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.

Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.

Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).

Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.

“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.

“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”

Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.

The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.

“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.

“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.

Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.

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

It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.

This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.

“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.

“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.

The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations

The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.

The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.

“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.

Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.

“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.

Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.

Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).

Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.

“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.

“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”

Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.

The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.

“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.

“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.

Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.

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

It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.

This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.

“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.

“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.

The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations

The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.

The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.

“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.

Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.

“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.

Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.

Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).

Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.

“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.

“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”

Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.

The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.

“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.

“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.

Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.

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

The influenza vaccine is linked to a significantly lower risk of ischemic stroke, with the reduced risk apparent at a population level even outside of flu season, in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.

“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.

Jovanmandic/Thinkstock

“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”

The study was published online in Neurology.
 

‘Not a spurious association’

While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.

In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.

Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).

Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).

Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).

The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.

The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.

Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).

“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
 

Anti-inflammatory effect?

Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.

The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.

“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.

In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.

“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.
 

‘More than just flu prevention’

In an accompanying editorial, Dixon Yang, MD, and Mitchell S.V. Elkind, MD, agree that the findings point to intriguing potential unexpected benefits of the vaccine.

“This case-control study ... importantly suggests the influenza vaccine is more than just about preventing the flu,” they wrote.

Dr. Elkind said in an interview that the mechanism could indeed involve an anti-inflammatory effect.

“There is some evidence that antibiotics also have anti-inflammatory properties that might reduce risk of stroke or the brain damage from a stroke,” he noted. “So, it is plausible that some of the effect of the vaccine on reducing risk of stroke may be through a reduction in inflammation.”

Dr. Elkind noted that the magnitude of the reduction observed with the vaccine, though not substantial, is important. “The magnitude of effect for any one individual may be modest, but it is in the ballpark of the effect of other commonly used approaches to stroke prevention, such as taking an aspirin a day, which reduces risk of stroke by about 20%. But because influenza is so common, the impact of even a small effect for an individual can have a large impact at the population level. So, the results are of public health significance.”

The study received support from the Biomedical Research Foundation of the Prince of Asturias University Hospital and the Institute of Health Carlos III in Madrid. Dr. Elkind has reported receiving ancillary funding but no personal compensation from Roche for a federally funded trial of stroke prevention.

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

The influenza vaccine is linked to a significantly lower risk of ischemic stroke, with the reduced risk apparent at a population level even outside of flu season, in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.

“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.

Jovanmandic/Thinkstock

“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”

The study was published online in Neurology.
 

‘Not a spurious association’

While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.

In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.

Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).

Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).

Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).

The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.

The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.

Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).

“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
 

Anti-inflammatory effect?

Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.

The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.

“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.

In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.

“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.
 

‘More than just flu prevention’

In an accompanying editorial, Dixon Yang, MD, and Mitchell S.V. Elkind, MD, agree that the findings point to intriguing potential unexpected benefits of the vaccine.

“This case-control study ... importantly suggests the influenza vaccine is more than just about preventing the flu,” they wrote.

Dr. Elkind said in an interview that the mechanism could indeed involve an anti-inflammatory effect.

“There is some evidence that antibiotics also have anti-inflammatory properties that might reduce risk of stroke or the brain damage from a stroke,” he noted. “So, it is plausible that some of the effect of the vaccine on reducing risk of stroke may be through a reduction in inflammation.”

Dr. Elkind noted that the magnitude of the reduction observed with the vaccine, though not substantial, is important. “The magnitude of effect for any one individual may be modest, but it is in the ballpark of the effect of other commonly used approaches to stroke prevention, such as taking an aspirin a day, which reduces risk of stroke by about 20%. But because influenza is so common, the impact of even a small effect for an individual can have a large impact at the population level. So, the results are of public health significance.”

The study received support from the Biomedical Research Foundation of the Prince of Asturias University Hospital and the Institute of Health Carlos III in Madrid. Dr. Elkind has reported receiving ancillary funding but no personal compensation from Roche for a federally funded trial of stroke prevention.

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

The influenza vaccine is linked to a significantly lower risk of ischemic stroke, with the reduced risk apparent at a population level even outside of flu season, in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.

“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.

Jovanmandic/Thinkstock

“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”

The study was published online in Neurology.
 

‘Not a spurious association’

While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.

In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.

Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).

Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).

Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).

The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.

The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.

Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).

“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
 

Anti-inflammatory effect?

Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.

The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.

“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.

In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.

“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.
 

‘More than just flu prevention’

In an accompanying editorial, Dixon Yang, MD, and Mitchell S.V. Elkind, MD, agree that the findings point to intriguing potential unexpected benefits of the vaccine.

“This case-control study ... importantly suggests the influenza vaccine is more than just about preventing the flu,” they wrote.

Dr. Elkind said in an interview that the mechanism could indeed involve an anti-inflammatory effect.

“There is some evidence that antibiotics also have anti-inflammatory properties that might reduce risk of stroke or the brain damage from a stroke,” he noted. “So, it is plausible that some of the effect of the vaccine on reducing risk of stroke may be through a reduction in inflammation.”

Dr. Elkind noted that the magnitude of the reduction observed with the vaccine, though not substantial, is important. “The magnitude of effect for any one individual may be modest, but it is in the ballpark of the effect of other commonly used approaches to stroke prevention, such as taking an aspirin a day, which reduces risk of stroke by about 20%. But because influenza is so common, the impact of even a small effect for an individual can have a large impact at the population level. So, the results are of public health significance.”

The study received support from the Biomedical Research Foundation of the Prince of Asturias University Hospital and the Institute of Health Carlos III in Madrid. Dr. Elkind has reported receiving ancillary funding but no personal compensation from Roche for a federally funded trial of stroke prevention.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

New data suggest that for individuals who do not have an adenoma detected on an index colonoscopy, the risk of developing an advanced neoplasia (AN) and colorectal cancer (CRC) is lower in those who are aged 40-49 years, compared with those who are 50-59 years old.

However, there is no difference between the two age groups in detection rates of nonadvanced adenoma (NAA) or advanced adenoma (AA), the same study found.

“The primary goal of this study was to investigate the risk of metachronous AN associated with conventional adenoma detected on the index colonoscopy,” explain the authors, led by Gene Ma, MD, Kaiser Permanente Northern California, San Jose.

“The lack of good-quality evidence to inform surveillance in the 40-49 year old population has resulted in inconsistent surveillance patterns in clinical practice, leading to variation in the quality of care, including both inadequate and excessive colonoscopic surveillance,” Dr. Ma and colleagues observe.

The findings from this study “expand our understanding of the risk of AN and CRC in younger individuals and suggest that the current multi-society guidelines for surveillance may be applicable for individuals 40-49 years of age,” the authors conclude.

The study was published online in The American Journal of Gastroenterology, and included 2,396 individuals between 40 and 49 years of age and 8,978 individuals between 50 and 59 years of age.

The colonoscopy was carried out for screening in 40.2% in the younger age group versus 34.8% in the older age group and was prompted by a positive fecal immunochemical test in 3.3% of the younger age group versus 32% of the older age group.

The median follow-up for both age groups was roughly 7 years.

“When comparing the 40-49 years group to the 50-59 years group, index colonoscopy detected no adenoma in 62.9% versus 40.1% (P < .0001); NAA in 25.4% versus 39.0% (P <.001), and AA in 11.6% versus 21.0% (P < .0001), respectively,” Dr. Ma and colleagues report.

When the two age groups were compared for surveillance colonoscopy, no adenoma was detected in 67% of the younger age group versus 54.7% of the older age group (P < .0001), whereas NAA was detected in 25.4% of the 40- to 49-year-olds versus 38.4% of the 50- to 59-year-olds (P < .0001). AA was detected in 3.5% versus 6.95 (P < .0001) of persons in each of the two age groups, respectively.

AN was detected on surveillance colonoscopy after index colonoscopy in 2.2% of the younger age group and twice that percentage, at 4.4%, in the older age group (P = .0003). On surveillance colonoscopy, NAA was found in 4.6% of the younger age group, compared with 7% of the older age group (P = .03), whereas AA was found in 7.9% of the 40- to 49-year-olds, compared with 11.7% of the 50- to 59-year-olds (P = .06).

The median time until surveillance colonoscopy was similar in both age groups when either NAA or AA was found on index colonoscopy, the authors note. In addition, the median time until the detection of AN was similar whether NAA or AA was detected on index colonoscopy, they add.

The overall crude cumulative incidence of AN was lower in the younger age group when no adenoma was detected on index colonoscopy (P = .0003) as well as when NAA was detected, which would be consistent with recommendations from current guidelines for surveillance colonoscopy after adenoma detection. However, there was no difference between the two age groups in the overall cumulative incidence of AN when AA was detected on index colonoscopy.

Overall, the risk for metachronous AN in persons aged 40-49 years was lower when no adenoma was detected on index colonoscopy, but there was no difference between the two age groups when NAA or AA was detected again on index colonoscopy. Similarly, those aged 40-49 years of age had a lower risk for AA or CRC when no adenoma was detected on index colonoscopy – but again, there was no difference in the risk for AA or CRC when either NAA or AA was detected on index colonoscopy.

The authors have no conflicts of interest to report.

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

New data suggest that for individuals who do not have an adenoma detected on an index colonoscopy, the risk of developing an advanced neoplasia (AN) and colorectal cancer (CRC) is lower in those who are aged 40-49 years, compared with those who are 50-59 years old.

However, there is no difference between the two age groups in detection rates of nonadvanced adenoma (NAA) or advanced adenoma (AA), the same study found.

“The primary goal of this study was to investigate the risk of metachronous AN associated with conventional adenoma detected on the index colonoscopy,” explain the authors, led by Gene Ma, MD, Kaiser Permanente Northern California, San Jose.

“The lack of good-quality evidence to inform surveillance in the 40-49 year old population has resulted in inconsistent surveillance patterns in clinical practice, leading to variation in the quality of care, including both inadequate and excessive colonoscopic surveillance,” Dr. Ma and colleagues observe.

The findings from this study “expand our understanding of the risk of AN and CRC in younger individuals and suggest that the current multi-society guidelines for surveillance may be applicable for individuals 40-49 years of age,” the authors conclude.

The study was published online in The American Journal of Gastroenterology, and included 2,396 individuals between 40 and 49 years of age and 8,978 individuals between 50 and 59 years of age.

The colonoscopy was carried out for screening in 40.2% in the younger age group versus 34.8% in the older age group and was prompted by a positive fecal immunochemical test in 3.3% of the younger age group versus 32% of the older age group.

The median follow-up for both age groups was roughly 7 years.

“When comparing the 40-49 years group to the 50-59 years group, index colonoscopy detected no adenoma in 62.9% versus 40.1% (P < .0001); NAA in 25.4% versus 39.0% (P <.001), and AA in 11.6% versus 21.0% (P < .0001), respectively,” Dr. Ma and colleagues report.

When the two age groups were compared for surveillance colonoscopy, no adenoma was detected in 67% of the younger age group versus 54.7% of the older age group (P < .0001), whereas NAA was detected in 25.4% of the 40- to 49-year-olds versus 38.4% of the 50- to 59-year-olds (P < .0001). AA was detected in 3.5% versus 6.95 (P < .0001) of persons in each of the two age groups, respectively.

AN was detected on surveillance colonoscopy after index colonoscopy in 2.2% of the younger age group and twice that percentage, at 4.4%, in the older age group (P = .0003). On surveillance colonoscopy, NAA was found in 4.6% of the younger age group, compared with 7% of the older age group (P = .03), whereas AA was found in 7.9% of the 40- to 49-year-olds, compared with 11.7% of the 50- to 59-year-olds (P = .06).

The median time until surveillance colonoscopy was similar in both age groups when either NAA or AA was found on index colonoscopy, the authors note. In addition, the median time until the detection of AN was similar whether NAA or AA was detected on index colonoscopy, they add.

The overall crude cumulative incidence of AN was lower in the younger age group when no adenoma was detected on index colonoscopy (P = .0003) as well as when NAA was detected, which would be consistent with recommendations from current guidelines for surveillance colonoscopy after adenoma detection. However, there was no difference between the two age groups in the overall cumulative incidence of AN when AA was detected on index colonoscopy.

Overall, the risk for metachronous AN in persons aged 40-49 years was lower when no adenoma was detected on index colonoscopy, but there was no difference between the two age groups when NAA or AA was detected again on index colonoscopy. Similarly, those aged 40-49 years of age had a lower risk for AA or CRC when no adenoma was detected on index colonoscopy – but again, there was no difference in the risk for AA or CRC when either NAA or AA was detected on index colonoscopy.

The authors have no conflicts of interest to report.

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

New data suggest that for individuals who do not have an adenoma detected on an index colonoscopy, the risk of developing an advanced neoplasia (AN) and colorectal cancer (CRC) is lower in those who are aged 40-49 years, compared with those who are 50-59 years old.

However, there is no difference between the two age groups in detection rates of nonadvanced adenoma (NAA) or advanced adenoma (AA), the same study found.

“The primary goal of this study was to investigate the risk of metachronous AN associated with conventional adenoma detected on the index colonoscopy,” explain the authors, led by Gene Ma, MD, Kaiser Permanente Northern California, San Jose.

“The lack of good-quality evidence to inform surveillance in the 40-49 year old population has resulted in inconsistent surveillance patterns in clinical practice, leading to variation in the quality of care, including both inadequate and excessive colonoscopic surveillance,” Dr. Ma and colleagues observe.

The findings from this study “expand our understanding of the risk of AN and CRC in younger individuals and suggest that the current multi-society guidelines for surveillance may be applicable for individuals 40-49 years of age,” the authors conclude.

The study was published online in The American Journal of Gastroenterology, and included 2,396 individuals between 40 and 49 years of age and 8,978 individuals between 50 and 59 years of age.

The colonoscopy was carried out for screening in 40.2% in the younger age group versus 34.8% in the older age group and was prompted by a positive fecal immunochemical test in 3.3% of the younger age group versus 32% of the older age group.

The median follow-up for both age groups was roughly 7 years.

“When comparing the 40-49 years group to the 50-59 years group, index colonoscopy detected no adenoma in 62.9% versus 40.1% (P < .0001); NAA in 25.4% versus 39.0% (P <.001), and AA in 11.6% versus 21.0% (P < .0001), respectively,” Dr. Ma and colleagues report.

When the two age groups were compared for surveillance colonoscopy, no adenoma was detected in 67% of the younger age group versus 54.7% of the older age group (P < .0001), whereas NAA was detected in 25.4% of the 40- to 49-year-olds versus 38.4% of the 50- to 59-year-olds (P < .0001). AA was detected in 3.5% versus 6.95 (P < .0001) of persons in each of the two age groups, respectively.

AN was detected on surveillance colonoscopy after index colonoscopy in 2.2% of the younger age group and twice that percentage, at 4.4%, in the older age group (P = .0003). On surveillance colonoscopy, NAA was found in 4.6% of the younger age group, compared with 7% of the older age group (P = .03), whereas AA was found in 7.9% of the 40- to 49-year-olds, compared with 11.7% of the 50- to 59-year-olds (P = .06).

The median time until surveillance colonoscopy was similar in both age groups when either NAA or AA was found on index colonoscopy, the authors note. In addition, the median time until the detection of AN was similar whether NAA or AA was detected on index colonoscopy, they add.

The overall crude cumulative incidence of AN was lower in the younger age group when no adenoma was detected on index colonoscopy (P = .0003) as well as when NAA was detected, which would be consistent with recommendations from current guidelines for surveillance colonoscopy after adenoma detection. However, there was no difference between the two age groups in the overall cumulative incidence of AN when AA was detected on index colonoscopy.

Overall, the risk for metachronous AN in persons aged 40-49 years was lower when no adenoma was detected on index colonoscopy, but there was no difference between the two age groups when NAA or AA was detected again on index colonoscopy. Similarly, those aged 40-49 years of age had a lower risk for AA or CRC when no adenoma was detected on index colonoscopy – but again, there was no difference in the risk for AA or CRC when either NAA or AA was detected on index colonoscopy.

The authors have no conflicts of interest to report.

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

Only one-third of pediatric dermatologists who prescribed isotretinoin for acne reported feeling confident in their understanding of emergency contraception (EC), in a survey of 57 clinicians.

Pregnancies among patients on isotretinoin have declined since the iPLEDGE risk management program was introduced in 2005, but from 2011 to 2017, 210 to 310 pregnancies were reported to the Food and Drug Administration every year, wrote Catherine E. Smiley of Penn State University, Hershey, Pa., and coauthors Melissa Butt, DrPH, and Andrea L. Zaenglein, MD, of Penn State.

For patients on isotretinoin, EC “becomes critical when abstinence fails or contraception is not used properly,” but EC merits only a brief mention in iPLEDGE materials for patients and providers, they noted.

Patients on isotretinoin who choose abstinence as their form of birth control are the group at greatest risk for pregnancy, Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, said in an interview. “However, the iPLEDGE program fails to educate patients adequately on emergency contraception,” she explained.

To assess pediatric dermatologists’ understanding of EC and their contraception counseling practices for isotretinoin patients, the researchers surveyed 57 pediatric dermatologists who prescribed isotretinoin as part of their practices. The findings were published in Pediatric Dermatology.Respondents included 53 practicing dermatologists, 2 residents, and 2 fellows. Approximately one-third (31.6%) had been in practice for 6-10 years, almost 23% had been in practice for 3-5 years, and almost 20% had been in practice for 21 or more years. Almost two-thirds practiced pediatric dermatology only.

Overall, 58% of the respondents strongly agreed that they provided contraception counseling to patients at their initial visit for isotretinoin, but only 7% and 3.5% reported providing EC counseling at initial and follow-up visits, respectively. More than half (58%) said they did not counsel patients on the side effects of EC.

As for provider education, 7.1% of respondents said they had received formal education on EC counseling, 25% reported receiving informal education on EC counseling, and 68% said they received no education on EC counseling.

A total of 32% of respondents said they were at least somewhat confident in how to obtain EC in their state.

EC is an effective form of contraception if used after unprotected intercourse, and discounts can reduce the price to as low as $9.69, the researchers wrote in their discussion. “Given that most providers in this study did not receive formal education on EC, and most do not provide EC counseling to their patients of reproductive potential on isotretinoin, EC education should be a core competency in dermatology residency education on isotretinoin prescribing,” the researchers noted. In addition, EC counseling in the iPLEDGE program should be improved by including more information in education materials and reminding patients that EC is an option, they said.

The study findings were limited by several factors including the small sample size and the multiple-choice format that prevented respondents to share rationales for their responses, the researchers noted.

However, the results highlight the need to improve EC education among pediatric dermatologists to better inform patients considering isotretinoin, especially those choosing abstinence as a method of birth control, they emphasized.

“This study is very important at this specific time for two reasons,” Dr. Zaenglein said in an interview. “The first is that with the recent disastrous rollout of the new iPLEDGE changes, there have been many calls to reform the REMS program. For the first time in the 22-year history of the program, the isotretinoin manufacturers, who manage the iPLEDGE program as an unidentified group (the IPMG), have been forced by the FDA to meet with the AAD iPLEDGE Task Force,” said Dr. Zaenglein, a member of the task force.

“The task force is currently advocating for common sense changes to iPLEDGE and I think enhancing education on emergency contraception is vital to the goal of the program, stated as ‘to manage the risk of isotretinoin’s teratogenicity and to minimize fetal exposure,’ ” she added. For many patients who previously became pregnant on isotretinoin, Plan B, an over-the-counter, FDA-approved form of contraception, might have prevented that pregnancy if the patients received adequate education on EC, she said.

The current study is especially relevant now, said Dr. Zaenglein. “With the reversal of Roe v. Wade, access to abortion is restricted or completely banned in many states, which makes educating our patients on how to prevent pregnancy even more important.”

Dr. Zaenglein said she was “somewhat surprised” by how many respondents were not educating their isotretinoin patients on EC. “However, these results follow a known trend among dermatologists. Only 50% of dermatologists prescribe oral contraceptives for acne, despite its being an FDA-approved treatment for the most common dermatologic condition we see in adolescents and young adults,” she noted.

“In general, dermatologists, and subsequently dermatology residents, are poorly educated on issues of reproductive health and how they are relevant to dermatologic care,” she added.

Dr. Zaenglein’s take home message: “Dermatologists should educate all patients of childbearing potential taking isotretinoin on how to acquire and use emergency contraception at every visit.” As for additional research, she said that since the study was conducted with pediatric dermatologists, “it would be very interesting to see if general dermatologists had the same lack of comfort in educating patients on emergency contraception and what their standard counseling practices are.”

The study received no outside funding. Dr. Zaenglein is a member of the AAD’s iPLEDGE Work Group and serves as an editor-in-chief of Pediatric Dermatology.

Only one-third of pediatric dermatologists who prescribed isotretinoin for acne reported feeling confident in their understanding of emergency contraception (EC), in a survey of 57 clinicians.

Pregnancies among patients on isotretinoin have declined since the iPLEDGE risk management program was introduced in 2005, but from 2011 to 2017, 210 to 310 pregnancies were reported to the Food and Drug Administration every year, wrote Catherine E. Smiley of Penn State University, Hershey, Pa., and coauthors Melissa Butt, DrPH, and Andrea L. Zaenglein, MD, of Penn State.

For patients on isotretinoin, EC “becomes critical when abstinence fails or contraception is not used properly,” but EC merits only a brief mention in iPLEDGE materials for patients and providers, they noted.

Patients on isotretinoin who choose abstinence as their form of birth control are the group at greatest risk for pregnancy, Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, said in an interview. “However, the iPLEDGE program fails to educate patients adequately on emergency contraception,” she explained.

To assess pediatric dermatologists’ understanding of EC and their contraception counseling practices for isotretinoin patients, the researchers surveyed 57 pediatric dermatologists who prescribed isotretinoin as part of their practices. The findings were published in Pediatric Dermatology.Respondents included 53 practicing dermatologists, 2 residents, and 2 fellows. Approximately one-third (31.6%) had been in practice for 6-10 years, almost 23% had been in practice for 3-5 years, and almost 20% had been in practice for 21 or more years. Almost two-thirds practiced pediatric dermatology only.

Overall, 58% of the respondents strongly agreed that they provided contraception counseling to patients at their initial visit for isotretinoin, but only 7% and 3.5% reported providing EC counseling at initial and follow-up visits, respectively. More than half (58%) said they did not counsel patients on the side effects of EC.

As for provider education, 7.1% of respondents said they had received formal education on EC counseling, 25% reported receiving informal education on EC counseling, and 68% said they received no education on EC counseling.

A total of 32% of respondents said they were at least somewhat confident in how to obtain EC in their state.

EC is an effective form of contraception if used after unprotected intercourse, and discounts can reduce the price to as low as $9.69, the researchers wrote in their discussion. “Given that most providers in this study did not receive formal education on EC, and most do not provide EC counseling to their patients of reproductive potential on isotretinoin, EC education should be a core competency in dermatology residency education on isotretinoin prescribing,” the researchers noted. In addition, EC counseling in the iPLEDGE program should be improved by including more information in education materials and reminding patients that EC is an option, they said.

The study findings were limited by several factors including the small sample size and the multiple-choice format that prevented respondents to share rationales for their responses, the researchers noted.

However, the results highlight the need to improve EC education among pediatric dermatologists to better inform patients considering isotretinoin, especially those choosing abstinence as a method of birth control, they emphasized.

“This study is very important at this specific time for two reasons,” Dr. Zaenglein said in an interview. “The first is that with the recent disastrous rollout of the new iPLEDGE changes, there have been many calls to reform the REMS program. For the first time in the 22-year history of the program, the isotretinoin manufacturers, who manage the iPLEDGE program as an unidentified group (the IPMG), have been forced by the FDA to meet with the AAD iPLEDGE Task Force,” said Dr. Zaenglein, a member of the task force.

“The task force is currently advocating for common sense changes to iPLEDGE and I think enhancing education on emergency contraception is vital to the goal of the program, stated as ‘to manage the risk of isotretinoin’s teratogenicity and to minimize fetal exposure,’ ” she added. For many patients who previously became pregnant on isotretinoin, Plan B, an over-the-counter, FDA-approved form of contraception, might have prevented that pregnancy if the patients received adequate education on EC, she said.

The current study is especially relevant now, said Dr. Zaenglein. “With the reversal of Roe v. Wade, access to abortion is restricted or completely banned in many states, which makes educating our patients on how to prevent pregnancy even more important.”

Dr. Zaenglein said she was “somewhat surprised” by how many respondents were not educating their isotretinoin patients on EC. “However, these results follow a known trend among dermatologists. Only 50% of dermatologists prescribe oral contraceptives for acne, despite its being an FDA-approved treatment for the most common dermatologic condition we see in adolescents and young adults,” she noted.

“In general, dermatologists, and subsequently dermatology residents, are poorly educated on issues of reproductive health and how they are relevant to dermatologic care,” she added.

Dr. Zaenglein’s take home message: “Dermatologists should educate all patients of childbearing potential taking isotretinoin on how to acquire and use emergency contraception at every visit.” As for additional research, she said that since the study was conducted with pediatric dermatologists, “it would be very interesting to see if general dermatologists had the same lack of comfort in educating patients on emergency contraception and what their standard counseling practices are.”

The study received no outside funding. Dr. Zaenglein is a member of the AAD’s iPLEDGE Work Group and serves as an editor-in-chief of Pediatric Dermatology.

Only one-third of pediatric dermatologists who prescribed isotretinoin for acne reported feeling confident in their understanding of emergency contraception (EC), in a survey of 57 clinicians.

Pregnancies among patients on isotretinoin have declined since the iPLEDGE risk management program was introduced in 2005, but from 2011 to 2017, 210 to 310 pregnancies were reported to the Food and Drug Administration every year, wrote Catherine E. Smiley of Penn State University, Hershey, Pa., and coauthors Melissa Butt, DrPH, and Andrea L. Zaenglein, MD, of Penn State.

For patients on isotretinoin, EC “becomes critical when abstinence fails or contraception is not used properly,” but EC merits only a brief mention in iPLEDGE materials for patients and providers, they noted.

Patients on isotretinoin who choose abstinence as their form of birth control are the group at greatest risk for pregnancy, Dr. Zaenglein, professor of dermatology and pediatric dermatology, Penn State University, said in an interview. “However, the iPLEDGE program fails to educate patients adequately on emergency contraception,” she explained.

To assess pediatric dermatologists’ understanding of EC and their contraception counseling practices for isotretinoin patients, the researchers surveyed 57 pediatric dermatologists who prescribed isotretinoin as part of their practices. The findings were published in Pediatric Dermatology.Respondents included 53 practicing dermatologists, 2 residents, and 2 fellows. Approximately one-third (31.6%) had been in practice for 6-10 years, almost 23% had been in practice for 3-5 years, and almost 20% had been in practice for 21 or more years. Almost two-thirds practiced pediatric dermatology only.

Overall, 58% of the respondents strongly agreed that they provided contraception counseling to patients at their initial visit for isotretinoin, but only 7% and 3.5% reported providing EC counseling at initial and follow-up visits, respectively. More than half (58%) said they did not counsel patients on the side effects of EC.

As for provider education, 7.1% of respondents said they had received formal education on EC counseling, 25% reported receiving informal education on EC counseling, and 68% said they received no education on EC counseling.

A total of 32% of respondents said they were at least somewhat confident in how to obtain EC in their state.

EC is an effective form of contraception if used after unprotected intercourse, and discounts can reduce the price to as low as $9.69, the researchers wrote in their discussion. “Given that most providers in this study did not receive formal education on EC, and most do not provide EC counseling to their patients of reproductive potential on isotretinoin, EC education should be a core competency in dermatology residency education on isotretinoin prescribing,” the researchers noted. In addition, EC counseling in the iPLEDGE program should be improved by including more information in education materials and reminding patients that EC is an option, they said.

The study findings were limited by several factors including the small sample size and the multiple-choice format that prevented respondents to share rationales for their responses, the researchers noted.

However, the results highlight the need to improve EC education among pediatric dermatologists to better inform patients considering isotretinoin, especially those choosing abstinence as a method of birth control, they emphasized.

“This study is very important at this specific time for two reasons,” Dr. Zaenglein said in an interview. “The first is that with the recent disastrous rollout of the new iPLEDGE changes, there have been many calls to reform the REMS program. For the first time in the 22-year history of the program, the isotretinoin manufacturers, who manage the iPLEDGE program as an unidentified group (the IPMG), have been forced by the FDA to meet with the AAD iPLEDGE Task Force,” said Dr. Zaenglein, a member of the task force.

“The task force is currently advocating for common sense changes to iPLEDGE and I think enhancing education on emergency contraception is vital to the goal of the program, stated as ‘to manage the risk of isotretinoin’s teratogenicity and to minimize fetal exposure,’ ” she added. For many patients who previously became pregnant on isotretinoin, Plan B, an over-the-counter, FDA-approved form of contraception, might have prevented that pregnancy if the patients received adequate education on EC, she said.

The current study is especially relevant now, said Dr. Zaenglein. “With the reversal of Roe v. Wade, access to abortion is restricted or completely banned in many states, which makes educating our patients on how to prevent pregnancy even more important.”

Dr. Zaenglein said she was “somewhat surprised” by how many respondents were not educating their isotretinoin patients on EC. “However, these results follow a known trend among dermatologists. Only 50% of dermatologists prescribe oral contraceptives for acne, despite its being an FDA-approved treatment for the most common dermatologic condition we see in adolescents and young adults,” she noted.

“In general, dermatologists, and subsequently dermatology residents, are poorly educated on issues of reproductive health and how they are relevant to dermatologic care,” she added.

Dr. Zaenglein’s take home message: “Dermatologists should educate all patients of childbearing potential taking isotretinoin on how to acquire and use emergency contraception at every visit.” As for additional research, she said that since the study was conducted with pediatric dermatologists, “it would be very interesting to see if general dermatologists had the same lack of comfort in educating patients on emergency contraception and what their standard counseling practices are.”

The study received no outside funding. Dr. Zaenglein is a member of the AAD’s iPLEDGE Work Group and serves as an editor-in-chief of Pediatric Dermatology.

Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.

Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.

“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.

However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.

The study was published online in Nature Genetics.

Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.

To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.

Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.

They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.

Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”

“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.

The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.

The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.

The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.

“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.

Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.

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

Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.

Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.

“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.

However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.

The study was published online in Nature Genetics.

Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.

To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.

Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.

They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.

Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”

“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.

The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.

The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.

The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.

“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.

Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.

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

Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.

Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.

“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.

However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.

The study was published online in Nature Genetics.

Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.

To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.

Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.

They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.

Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”

“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.

The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.

The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.

The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.

“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.

Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.

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

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Intestinal ultrasound (IUS) findings correlate strongly with endoscopy results in patients with ulcerative colitis (UC), with treatment responses detected as soon as 8 weeks after starting tofacitinib, a longitudinal prospective study has found.

IUS accurately detected improvements and remission across a variety of scoring methodologies, suggesting that it may be a cost-effective, noninvasive alternative to endoscopic monitoring, reported lead author Floris de Voogd, MD, of Amsterdam University Medical Centers, and colleagues.

“Endoscopy is generally considered as the gold standard for the diagnosis and follow-up of patients with UC,” the investigators wrote in Gastroenterology. “However, endoscopy is an invasive and costly modality and therefore less attractive to perform frequently during the disease course.”

Whereas noninvasive fecal biomarkers are a more economical method of monitoring inflammation and treatment responses, they fail to characterize disease extent and fall short in detecting early endoscopic responses, the investigators added.

The present study aimed to determine if IUS could offer more clinical insight by measuring bowel wall thickness. Thirty patients were enrolled with moderate to severe UC, all with an endoscopic Mayo score of at least 2. Twenty-seven of these patients were evaluable through follow-up, having undergone both IUS and endoscopy at baseline and 8 weeks after starting tofacitinib.

At both time points, IUS findings correlated significantly with endoscopic Mayo score (EMS), UC endoscopic index for severity, and Robarts Histopathology Index, with correlation coefficients of 0.68, 0.73, and 0.49, respectively. Remission according to EMS was defined as a score of 0, and improvement was defined as a score of 1 or less.

Patients with EMS improvement showed lower median bowel wall thickness in the sigmoid colon after 8 weeks of treatment than did patients without improvement (1.8 mm vs. 4.5 mm; P < .0001); patients who were in EMS remission after 8 weeks also had lower median bowel wall thickness of the sigmoid colon (1.4 mm vs. 4.0 mm; P = .016).

The investigators also sought to define cutoff values for bowel wall thickness. The most accurate cutoff values for identifying endoscopic remission and improvement were 2.8 mm (area under the receiver operating curve, 0.87; 95% confidence interval, 0.74-1.00; P = .006) and 3.9 mm (AUROC, 0.92; 95% CI, 0.82-1.00; P < .0001), respectively. Treatment response was best identified by a 32% threshold reduction in thickness (AUROC, 0.87; 95% CI, 0.74-1.00; P = .002).

“Intestinal ultrasound, with bowel wall thickness as the single most important parameter is accurate to determine treatment response to tofacitinib in patients with moderate-severe UC when compared against endoscopy,” the investigators concluded.

Michael Dolinger, MD, MBA, assistant professor of pediatrics and the associate pediatric gastroenterology fellowship program director at the Icahn School of Medicine at Mount Sinai, New York, said the study is noteworthy because it is the first of its kind to show that IUS can accurately monitor treatment responses in UC.

“This study is what we’re looking for now, and in the future,” Dr. Dolinger said in an interview. “We’re looking for noninvasive biomarkers to predict early responses so that we know as clinicians ... if our medicines are working or if we need to pivot and switch effectively.”

For patients, this can mean feeling better quicker while reducing burden of care, he added.

“We can use this study to predict patient responses without having to potentially rescope them in 8 weeks using a 5-minute point-of-care test in the clinic,” Dr. Dolinger said. “It’s huge to be able to say that for patients with colitis, and to provide reassurance that not only are they potentially feeling better, but the medicine is working to change and heal their bowel wall really quickly as well.”

Dr. Dolinger speaks from clinical experience. Over the past 2 years, he and his colleagues at Mount Sinai have been implementing IUS for patients with both UC and Crohn’s disease.

“It’s become part of our standard of care,” Dr. Dolinger said. “This is now emerging in the United States and will soon take hold. There is a lot of interest.”

Dr. Dolinger is one of just a few American physicians credentialed by the International Bowel Ultrasound Group, an organization based out of Europe, Israel, and Canada. Formalized training and certification are necessary, Dr. Dolinger noted, to ensure that this new clinical approach maintains consistency as it is rolled out across the United States.

“We have the unique opportunity to do something from the ground up quickly, but also correctly, meaning that we can train everyone to speak the same language and do the same standardized exams so that all the findings and research are relatable,” Dr. Dolinger said.

He advised interested physicians to contact their local inflammatory bowel disease center to find out if training is available, and if it is, devoting “a lot of time” to the learning process.

“If you’re going to use this potentially as a clinical decision-making tool without using other invasive procedures, you really want to make sure what you’re doing is accurate and correct,” Dr. Dolinger said.

The investigators disclosed relationships with AbbVie, Merck, Takeda, and others. Dr. Dolinger disclosed a relationship with NeuroLogica, a subsidiary of Samsung Electronics.

Intestinal ultrasound (IUS) findings correlate strongly with endoscopy results in patients with ulcerative colitis (UC), with treatment responses detected as soon as 8 weeks after starting tofacitinib, a longitudinal prospective study has found.

IUS accurately detected improvements and remission across a variety of scoring methodologies, suggesting that it may be a cost-effective, noninvasive alternative to endoscopic monitoring, reported lead author Floris de Voogd, MD, of Amsterdam University Medical Centers, and colleagues.

“Endoscopy is generally considered as the gold standard for the diagnosis and follow-up of patients with UC,” the investigators wrote in Gastroenterology. “However, endoscopy is an invasive and costly modality and therefore less attractive to perform frequently during the disease course.”

Whereas noninvasive fecal biomarkers are a more economical method of monitoring inflammation and treatment responses, they fail to characterize disease extent and fall short in detecting early endoscopic responses, the investigators added.

The present study aimed to determine if IUS could offer more clinical insight by measuring bowel wall thickness. Thirty patients were enrolled with moderate to severe UC, all with an endoscopic Mayo score of at least 2. Twenty-seven of these patients were evaluable through follow-up, having undergone both IUS and endoscopy at baseline and 8 weeks after starting tofacitinib.

At both time points, IUS findings correlated significantly with endoscopic Mayo score (EMS), UC endoscopic index for severity, and Robarts Histopathology Index, with correlation coefficients of 0.68, 0.73, and 0.49, respectively. Remission according to EMS was defined as a score of 0, and improvement was defined as a score of 1 or less.

Patients with EMS improvement showed lower median bowel wall thickness in the sigmoid colon after 8 weeks of treatment than did patients without improvement (1.8 mm vs. 4.5 mm; P < .0001); patients who were in EMS remission after 8 weeks also had lower median bowel wall thickness of the sigmoid colon (1.4 mm vs. 4.0 mm; P = .016).

The investigators also sought to define cutoff values for bowel wall thickness. The most accurate cutoff values for identifying endoscopic remission and improvement were 2.8 mm (area under the receiver operating curve, 0.87; 95% confidence interval, 0.74-1.00; P = .006) and 3.9 mm (AUROC, 0.92; 95% CI, 0.82-1.00; P < .0001), respectively. Treatment response was best identified by a 32% threshold reduction in thickness (AUROC, 0.87; 95% CI, 0.74-1.00; P = .002).

“Intestinal ultrasound, with bowel wall thickness as the single most important parameter is accurate to determine treatment response to tofacitinib in patients with moderate-severe UC when compared against endoscopy,” the investigators concluded.

Michael Dolinger, MD, MBA, assistant professor of pediatrics and the associate pediatric gastroenterology fellowship program director at the Icahn School of Medicine at Mount Sinai, New York, said the study is noteworthy because it is the first of its kind to show that IUS can accurately monitor treatment responses in UC.

“This study is what we’re looking for now, and in the future,” Dr. Dolinger said in an interview. “We’re looking for noninvasive biomarkers to predict early responses so that we know as clinicians ... if our medicines are working or if we need to pivot and switch effectively.”

For patients, this can mean feeling better quicker while reducing burden of care, he added.

“We can use this study to predict patient responses without having to potentially rescope them in 8 weeks using a 5-minute point-of-care test in the clinic,” Dr. Dolinger said. “It’s huge to be able to say that for patients with colitis, and to provide reassurance that not only are they potentially feeling better, but the medicine is working to change and heal their bowel wall really quickly as well.”

Dr. Dolinger speaks from clinical experience. Over the past 2 years, he and his colleagues at Mount Sinai have been implementing IUS for patients with both UC and Crohn’s disease.

“It’s become part of our standard of care,” Dr. Dolinger said. “This is now emerging in the United States and will soon take hold. There is a lot of interest.”

Dr. Dolinger is one of just a few American physicians credentialed by the International Bowel Ultrasound Group, an organization based out of Europe, Israel, and Canada. Formalized training and certification are necessary, Dr. Dolinger noted, to ensure that this new clinical approach maintains consistency as it is rolled out across the United States.

“We have the unique opportunity to do something from the ground up quickly, but also correctly, meaning that we can train everyone to speak the same language and do the same standardized exams so that all the findings and research are relatable,” Dr. Dolinger said.

He advised interested physicians to contact their local inflammatory bowel disease center to find out if training is available, and if it is, devoting “a lot of time” to the learning process.

“If you’re going to use this potentially as a clinical decision-making tool without using other invasive procedures, you really want to make sure what you’re doing is accurate and correct,” Dr. Dolinger said.

The investigators disclosed relationships with AbbVie, Merck, Takeda, and others. Dr. Dolinger disclosed a relationship with NeuroLogica, a subsidiary of Samsung Electronics.

Intestinal ultrasound (IUS) findings correlate strongly with endoscopy results in patients with ulcerative colitis (UC), with treatment responses detected as soon as 8 weeks after starting tofacitinib, a longitudinal prospective study has found.

IUS accurately detected improvements and remission across a variety of scoring methodologies, suggesting that it may be a cost-effective, noninvasive alternative to endoscopic monitoring, reported lead author Floris de Voogd, MD, of Amsterdam University Medical Centers, and colleagues.

“Endoscopy is generally considered as the gold standard for the diagnosis and follow-up of patients with UC,” the investigators wrote in Gastroenterology. “However, endoscopy is an invasive and costly modality and therefore less attractive to perform frequently during the disease course.”

Whereas noninvasive fecal biomarkers are a more economical method of monitoring inflammation and treatment responses, they fail to characterize disease extent and fall short in detecting early endoscopic responses, the investigators added.

The present study aimed to determine if IUS could offer more clinical insight by measuring bowel wall thickness. Thirty patients were enrolled with moderate to severe UC, all with an endoscopic Mayo score of at least 2. Twenty-seven of these patients were evaluable through follow-up, having undergone both IUS and endoscopy at baseline and 8 weeks after starting tofacitinib.

At both time points, IUS findings correlated significantly with endoscopic Mayo score (EMS), UC endoscopic index for severity, and Robarts Histopathology Index, with correlation coefficients of 0.68, 0.73, and 0.49, respectively. Remission according to EMS was defined as a score of 0, and improvement was defined as a score of 1 or less.

Patients with EMS improvement showed lower median bowel wall thickness in the sigmoid colon after 8 weeks of treatment than did patients without improvement (1.8 mm vs. 4.5 mm; P < .0001); patients who were in EMS remission after 8 weeks also had lower median bowel wall thickness of the sigmoid colon (1.4 mm vs. 4.0 mm; P = .016).

The investigators also sought to define cutoff values for bowel wall thickness. The most accurate cutoff values for identifying endoscopic remission and improvement were 2.8 mm (area under the receiver operating curve, 0.87; 95% confidence interval, 0.74-1.00; P = .006) and 3.9 mm (AUROC, 0.92; 95% CI, 0.82-1.00; P < .0001), respectively. Treatment response was best identified by a 32% threshold reduction in thickness (AUROC, 0.87; 95% CI, 0.74-1.00; P = .002).

“Intestinal ultrasound, with bowel wall thickness as the single most important parameter is accurate to determine treatment response to tofacitinib in patients with moderate-severe UC when compared against endoscopy,” the investigators concluded.

Michael Dolinger, MD, MBA, assistant professor of pediatrics and the associate pediatric gastroenterology fellowship program director at the Icahn School of Medicine at Mount Sinai, New York, said the study is noteworthy because it is the first of its kind to show that IUS can accurately monitor treatment responses in UC.

“This study is what we’re looking for now, and in the future,” Dr. Dolinger said in an interview. “We’re looking for noninvasive biomarkers to predict early responses so that we know as clinicians ... if our medicines are working or if we need to pivot and switch effectively.”

For patients, this can mean feeling better quicker while reducing burden of care, he added.

“We can use this study to predict patient responses without having to potentially rescope them in 8 weeks using a 5-minute point-of-care test in the clinic,” Dr. Dolinger said. “It’s huge to be able to say that for patients with colitis, and to provide reassurance that not only are they potentially feeling better, but the medicine is working to change and heal their bowel wall really quickly as well.”

Dr. Dolinger speaks from clinical experience. Over the past 2 years, he and his colleagues at Mount Sinai have been implementing IUS for patients with both UC and Crohn’s disease.

“It’s become part of our standard of care,” Dr. Dolinger said. “This is now emerging in the United States and will soon take hold. There is a lot of interest.”

Dr. Dolinger is one of just a few American physicians credentialed by the International Bowel Ultrasound Group, an organization based out of Europe, Israel, and Canada. Formalized training and certification are necessary, Dr. Dolinger noted, to ensure that this new clinical approach maintains consistency as it is rolled out across the United States.

“We have the unique opportunity to do something from the ground up quickly, but also correctly, meaning that we can train everyone to speak the same language and do the same standardized exams so that all the findings and research are relatable,” Dr. Dolinger said.

He advised interested physicians to contact their local inflammatory bowel disease center to find out if training is available, and if it is, devoting “a lot of time” to the learning process.

“If you’re going to use this potentially as a clinical decision-making tool without using other invasive procedures, you really want to make sure what you’re doing is accurate and correct,” Dr. Dolinger said.

The investigators disclosed relationships with AbbVie, Merck, Takeda, and others. Dr. Dolinger disclosed a relationship with NeuroLogica, a subsidiary of Samsung Electronics.