Federal Practitioner

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

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

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

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

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

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

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

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

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

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

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

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

LAS VEGAS –Data from the 28-week extension of the Liberty EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Many patients don’t respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab’s effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.

“The current treatments are [proton pump inhibitors], steroids, or diet – a good proportion of patients don’t respond to them. And they’re also not targeted,” Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dr. Dellon presented the research at the annual meeting of the American College of Gastroenterology.

“The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes,” said Dr. Dellon.

Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dr. Dellon. “You can’t compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it’s a harder to treat cohort is pretty impressive from that standpoint,” said Dr. Dellon.

Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.

At ACG 2021, Dr. Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs. –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% versus 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).

The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs. 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.

Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs. –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs. –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).

Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 versus –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).

Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.

“I thought the data was really impressive and compelling,” said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who comoderated the session. “It’d be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term.”

If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said comoderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.

One concern with dupilumab would be any potential for immune suppression. “It’s always something to think about,” Dr. Hass said.

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon has consulted and received research support from numerous pharmaceutical companies. Dr. Oxentenko and Dr. Hass have no relevant financial disclosures.

This article was updated Nov. 4, 2021.

LAS VEGAS –Data from the 28-week extension of the Liberty EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Many patients don’t respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab’s effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.

“The current treatments are [proton pump inhibitors], steroids, or diet – a good proportion of patients don’t respond to them. And they’re also not targeted,” Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dr. Dellon presented the research at the annual meeting of the American College of Gastroenterology.

“The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes,” said Dr. Dellon.

Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dr. Dellon. “You can’t compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it’s a harder to treat cohort is pretty impressive from that standpoint,” said Dr. Dellon.

Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.

At ACG 2021, Dr. Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs. –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% versus 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).

The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs. 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.

Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs. –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs. –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).

Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 versus –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).

Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.

“I thought the data was really impressive and compelling,” said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who comoderated the session. “It’d be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term.”

If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said comoderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.

One concern with dupilumab would be any potential for immune suppression. “It’s always something to think about,” Dr. Hass said.

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon has consulted and received research support from numerous pharmaceutical companies. Dr. Oxentenko and Dr. Hass have no relevant financial disclosures.

This article was updated Nov. 4, 2021.

LAS VEGAS –Data from the 28-week extension of the Liberty EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Many patients don’t respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab’s effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.

“The current treatments are [proton pump inhibitors], steroids, or diet – a good proportion of patients don’t respond to them. And they’re also not targeted,” Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dr. Dellon presented the research at the annual meeting of the American College of Gastroenterology.

“The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes,” said Dr. Dellon.

Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dr. Dellon. “You can’t compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it’s a harder to treat cohort is pretty impressive from that standpoint,” said Dr. Dellon.

Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.

At ACG 2021, Dr. Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs. –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% versus 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).

The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs. 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.

Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs. –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs. –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).

Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 versus –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).

Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.

“I thought the data was really impressive and compelling,” said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who comoderated the session. “It’d be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term.”

If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said comoderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.

One concern with dupilumab would be any potential for immune suppression. “It’s always something to think about,” Dr. Hass said.

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon has consulted and received research support from numerous pharmaceutical companies. Dr. Oxentenko and Dr. Hass have no relevant financial disclosures.

This article was updated Nov. 4, 2021.

The number of adenomas per colonoscopy (APC) is inversely correlated with postcolonoscopy colorectal cancer (PCCRC), which supports use of APC as a new quality control measure, according to investigators.

Data from 138 endoscopists showed that patients screened by physicians with higher APCs had significantly lower rates of PCCRC, and an APC of 0.6 offered more protection than either an APC of 0.4 or an adenoma detection rate (ADR) of 25%, reported lead author Joseph C. Anderson, MD, of White River Junction VA Medical Center, Hanover, N.H., and colleagues.

“Unfortunately, APC has never been validated as a quality measure by demonstrating a reduction in PCCRC in exams performed by endoscopists with higher rates,” Dr. Anderson said at the annual meeting of the American College of Gastroenterology.

To this end, Dr. Anderson and colleagues reviewed data from the New Hampshire Colonoscopy Registry (NHCR), including 9,023 screening colonoscopies with a follow-up event 6-60 months after the initial exam. Procedures were conducted by 138 endoscopists in New Hampshire, Vermont, Massachusetts, and Maine.

Three quality measures were analyzed for associations with PCCRC: an APC of 0.4, an APC of 0.6, and an ADR of 25%. Hazard ratios were calculated for all PCCRCs, as well as PCCRCs diagnosed at first follow-up event. Rates were reported for two time periods: 6-36 months and 6-60 months.

From 6 to 60 months, 82 cases of PCCRC were diagnosed, among which 50 were diagnosed between 6 and 36 months.

For both periods, all three quality measures were significantly associated with reductions in PCCRC. The higher APC of 0.6, however, offered greater protection, reducing all PCCRCs by 71% and 61% in the shorter and longer period, respectively. In comparison, the lower APC of 0.4 reduced rates by 63% and 53%, while the ADR benchmark reduced rates by 62% and 42%.

These trends were maintained for PCCRCs diagnosed at first follow-up event. An APC of 0.6 was associated with respective reductions of 79% and 65% for the shorter and longer period, compared with 64% and 57% for the lower APC, and 67% and 49% for ADR.

Additional analysis clarified the relationship between APC level and likelihood of developing PCCRC. In terms of absolute risk, patients screened by an endoscopist with an APC greater than 0.6 had a 0.5% chance of developing PCCRC from 6 to 36 months, compared with 0.7% for an APC of 0.4-0.6, and 2.1% for an APC of less than 0.4 (P = .0001). This pattern held through 60 months, during which time an APC greater than 0.6 was associated with an absolute risk of PCCRC of 0.4%, compared with 0.7% for an APC of 0.4-0.6, and 1.6% for an APC less than 0.4 (P = .0001).

“Our novel data support the use of APC as a quality measure by demonstrating a reduction in PCCRC risk in exams performed by endoscopists with higher APCs,” Dr. Anderson concluded, noting that an APC of 0.6 appeared to offer more protection than an APC of 0.4. “I feel that ... APC as a quality measure, now that we’ve validated it, may be accepted because of its ability to differentiate endoscopists on their adenoma detection skills.”

According to Lawrence Hookey, MD, of Queen’s University, Kingston, Ont., “It’s an important study that will probably contribute to where we’re going forward.”

Dr. Lawrence, chair of the division and medical director of the endoscopy units at Kingston General and Hotel Dieu hospitals, said that APC may overcome the main concern with ADR – that endoscopists who find one adenoma may not be motivated to seek out as many as possible.

“The problem with ADR, in general, is that if you find one polyp, and if ADR is the stat you’re living by, then you don’t need to find any other polyps, and that obviously doesn’t do that patient a favor, necessarily,” Dr. Hookey said in an interview. “It does bring them back sooner for surveillance, but it doesn’t help remove the rest of the polyps that they have. And not that someone is going to find one polyp and turn off the light and pull the scope out, but you may not be looking as hard.”

APC mitigates this issue, he explained, because it determines “whether or not you’re truly clearing things out and getting rid of as many [polyps] as possible.”

Dr. Hookey said that APC is “probably the best” quality control measure on the horizon, and he suggested that more work is needed to determine the optimal benchmark figure, which should ideally be investigated through larger studies.

“I just want to see it in bigger groups,” he said.

The investigators and Dr. Hookey reported no conflicts of interest.

The number of adenomas per colonoscopy (APC) is inversely correlated with postcolonoscopy colorectal cancer (PCCRC), which supports use of APC as a new quality control measure, according to investigators.

Data from 138 endoscopists showed that patients screened by physicians with higher APCs had significantly lower rates of PCCRC, and an APC of 0.6 offered more protection than either an APC of 0.4 or an adenoma detection rate (ADR) of 25%, reported lead author Joseph C. Anderson, MD, of White River Junction VA Medical Center, Hanover, N.H., and colleagues.

“Unfortunately, APC has never been validated as a quality measure by demonstrating a reduction in PCCRC in exams performed by endoscopists with higher rates,” Dr. Anderson said at the annual meeting of the American College of Gastroenterology.

To this end, Dr. Anderson and colleagues reviewed data from the New Hampshire Colonoscopy Registry (NHCR), including 9,023 screening colonoscopies with a follow-up event 6-60 months after the initial exam. Procedures were conducted by 138 endoscopists in New Hampshire, Vermont, Massachusetts, and Maine.

Three quality measures were analyzed for associations with PCCRC: an APC of 0.4, an APC of 0.6, and an ADR of 25%. Hazard ratios were calculated for all PCCRCs, as well as PCCRCs diagnosed at first follow-up event. Rates were reported for two time periods: 6-36 months and 6-60 months.

From 6 to 60 months, 82 cases of PCCRC were diagnosed, among which 50 were diagnosed between 6 and 36 months.

For both periods, all three quality measures were significantly associated with reductions in PCCRC. The higher APC of 0.6, however, offered greater protection, reducing all PCCRCs by 71% and 61% in the shorter and longer period, respectively. In comparison, the lower APC of 0.4 reduced rates by 63% and 53%, while the ADR benchmark reduced rates by 62% and 42%.

These trends were maintained for PCCRCs diagnosed at first follow-up event. An APC of 0.6 was associated with respective reductions of 79% and 65% for the shorter and longer period, compared with 64% and 57% for the lower APC, and 67% and 49% for ADR.

Additional analysis clarified the relationship between APC level and likelihood of developing PCCRC. In terms of absolute risk, patients screened by an endoscopist with an APC greater than 0.6 had a 0.5% chance of developing PCCRC from 6 to 36 months, compared with 0.7% for an APC of 0.4-0.6, and 2.1% for an APC of less than 0.4 (P = .0001). This pattern held through 60 months, during which time an APC greater than 0.6 was associated with an absolute risk of PCCRC of 0.4%, compared with 0.7% for an APC of 0.4-0.6, and 1.6% for an APC less than 0.4 (P = .0001).

“Our novel data support the use of APC as a quality measure by demonstrating a reduction in PCCRC risk in exams performed by endoscopists with higher APCs,” Dr. Anderson concluded, noting that an APC of 0.6 appeared to offer more protection than an APC of 0.4. “I feel that ... APC as a quality measure, now that we’ve validated it, may be accepted because of its ability to differentiate endoscopists on their adenoma detection skills.”

According to Lawrence Hookey, MD, of Queen’s University, Kingston, Ont., “It’s an important study that will probably contribute to where we’re going forward.”

Dr. Lawrence, chair of the division and medical director of the endoscopy units at Kingston General and Hotel Dieu hospitals, said that APC may overcome the main concern with ADR – that endoscopists who find one adenoma may not be motivated to seek out as many as possible.

“The problem with ADR, in general, is that if you find one polyp, and if ADR is the stat you’re living by, then you don’t need to find any other polyps, and that obviously doesn’t do that patient a favor, necessarily,” Dr. Hookey said in an interview. “It does bring them back sooner for surveillance, but it doesn’t help remove the rest of the polyps that they have. And not that someone is going to find one polyp and turn off the light and pull the scope out, but you may not be looking as hard.”

APC mitigates this issue, he explained, because it determines “whether or not you’re truly clearing things out and getting rid of as many [polyps] as possible.”

Dr. Hookey said that APC is “probably the best” quality control measure on the horizon, and he suggested that more work is needed to determine the optimal benchmark figure, which should ideally be investigated through larger studies.

“I just want to see it in bigger groups,” he said.

The investigators and Dr. Hookey reported no conflicts of interest.

The number of adenomas per colonoscopy (APC) is inversely correlated with postcolonoscopy colorectal cancer (PCCRC), which supports use of APC as a new quality control measure, according to investigators.

Data from 138 endoscopists showed that patients screened by physicians with higher APCs had significantly lower rates of PCCRC, and an APC of 0.6 offered more protection than either an APC of 0.4 or an adenoma detection rate (ADR) of 25%, reported lead author Joseph C. Anderson, MD, of White River Junction VA Medical Center, Hanover, N.H., and colleagues.

“Unfortunately, APC has never been validated as a quality measure by demonstrating a reduction in PCCRC in exams performed by endoscopists with higher rates,” Dr. Anderson said at the annual meeting of the American College of Gastroenterology.

To this end, Dr. Anderson and colleagues reviewed data from the New Hampshire Colonoscopy Registry (NHCR), including 9,023 screening colonoscopies with a follow-up event 6-60 months after the initial exam. Procedures were conducted by 138 endoscopists in New Hampshire, Vermont, Massachusetts, and Maine.

Three quality measures were analyzed for associations with PCCRC: an APC of 0.4, an APC of 0.6, and an ADR of 25%. Hazard ratios were calculated for all PCCRCs, as well as PCCRCs diagnosed at first follow-up event. Rates were reported for two time periods: 6-36 months and 6-60 months.

From 6 to 60 months, 82 cases of PCCRC were diagnosed, among which 50 were diagnosed between 6 and 36 months.

For both periods, all three quality measures were significantly associated with reductions in PCCRC. The higher APC of 0.6, however, offered greater protection, reducing all PCCRCs by 71% and 61% in the shorter and longer period, respectively. In comparison, the lower APC of 0.4 reduced rates by 63% and 53%, while the ADR benchmark reduced rates by 62% and 42%.

These trends were maintained for PCCRCs diagnosed at first follow-up event. An APC of 0.6 was associated with respective reductions of 79% and 65% for the shorter and longer period, compared with 64% and 57% for the lower APC, and 67% and 49% for ADR.

Additional analysis clarified the relationship between APC level and likelihood of developing PCCRC. In terms of absolute risk, patients screened by an endoscopist with an APC greater than 0.6 had a 0.5% chance of developing PCCRC from 6 to 36 months, compared with 0.7% for an APC of 0.4-0.6, and 2.1% for an APC of less than 0.4 (P = .0001). This pattern held through 60 months, during which time an APC greater than 0.6 was associated with an absolute risk of PCCRC of 0.4%, compared with 0.7% for an APC of 0.4-0.6, and 1.6% for an APC less than 0.4 (P = .0001).

“Our novel data support the use of APC as a quality measure by demonstrating a reduction in PCCRC risk in exams performed by endoscopists with higher APCs,” Dr. Anderson concluded, noting that an APC of 0.6 appeared to offer more protection than an APC of 0.4. “I feel that ... APC as a quality measure, now that we’ve validated it, may be accepted because of its ability to differentiate endoscopists on their adenoma detection skills.”

According to Lawrence Hookey, MD, of Queen’s University, Kingston, Ont., “It’s an important study that will probably contribute to where we’re going forward.”

Dr. Lawrence, chair of the division and medical director of the endoscopy units at Kingston General and Hotel Dieu hospitals, said that APC may overcome the main concern with ADR – that endoscopists who find one adenoma may not be motivated to seek out as many as possible.

“The problem with ADR, in general, is that if you find one polyp, and if ADR is the stat you’re living by, then you don’t need to find any other polyps, and that obviously doesn’t do that patient a favor, necessarily,” Dr. Hookey said in an interview. “It does bring them back sooner for surveillance, but it doesn’t help remove the rest of the polyps that they have. And not that someone is going to find one polyp and turn off the light and pull the scope out, but you may not be looking as hard.”

APC mitigates this issue, he explained, because it determines “whether or not you’re truly clearing things out and getting rid of as many [polyps] as possible.”

Dr. Hookey said that APC is “probably the best” quality control measure on the horizon, and he suggested that more work is needed to determine the optimal benchmark figure, which should ideally be investigated through larger studies.

“I just want to see it in bigger groups,” he said.

The investigators and Dr. Hookey reported no conflicts of interest.

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does not appear to raise the risk for fractures in older adults, new research suggests.

The data come from a nationwide propensity score-matched study of U.S. Medicare recipients with type 2 diabetes who were new users of either an SGLT2 inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors was not associated with an increased risk of nontraumatic fractures compared with DPP-4 inhibitors or GLP-1 agonists. Results were consistent across categories of sex, frailty, age, and insulin use,” say Min Zhuo, MD, of Harvard Medical School, Boston, and colleagues, who published their work online October 27 in JAMA Network Open.

“Our results add to the evidence base evaluating the safety profile of SGLT2 inhibitors in older adults outside of [randomized controlled trials] and further characterize the risk-benefit balance of SGLT2 inhibitors in clinical practice,” they write.

Asked to comment, Simeon I. Taylor, MD, PhD, told this news organization, “This is a high-quality study that is generally reassuring that relatively short, less than 1 year, treatment with an SGLT2 inhibitor does not appear to significantly increase the risk of bone fractures.”

However, Dr. Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, also noted: “Notwithstanding these reassuring data, the paper also does a good job of pointing out important limitations.”

“Most importantly, these data do not address questions related to the risk of long-term chronic therapy. It is instructive to refer back to the published data demonstrating an approximately 2-year lag before a significant increase in the risk of fracture was observed in rosiglitazone-treated patients in the ADOPT study. The length of the lag is likely related to the baseline bone mineral density at the time drug therapy is initiated. These considerations may contribute to the observed variation in bone-related outcomes in different studies.”

Concern about SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS study, in which the overall fracture risk with canagliflozin was a significant 26% higher than placebo. However, subsequent larger randomized trials of canagliflozin and other SGLT2 inhibitors did not find the same risk.

In addition, previous observational studies in younger adults have also not found use of SGLT2 inhibitors to be associated with increased fracture risk compared with DPP-4 inhibitors or GLP-1 agonists.
 

Understanding fracture risk with SGLT2 inhibitors is ‘critical’

Older adults with type 2 diabetes may benefit from reductions in atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death associated with SGLT2 inhibitors, but the fact that aging may have negative effects on bone metabolism means “understanding the fracture risk associated with SGLT2 inhibitors in older adults with type 2 diabetes is critical,” say Dr. Zhuo and colleagues.

In the current study, they analyzed claims data for Medicare beneficiaries aged 66 years and older (1 year past Medicare eligibility) who were newly prescribed an SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1 agonist between April 1, 2013 and Dec. 31, 2017.

A total of 45,889 patients from each treatment group were propensity-matched using 58 baseline characteristics, for a total of 137,667 patients.

After matching, there were 501 events of the primary composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By treatment group, fracture rates per 1,000 person-years were 4.69, 5.26, and 4.71 for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists respectively.

The differences between patients taking DPP-4 inhibitors or GLP-1 agonists compared with SGLT2 inhibitors were not significant, with hazard ratios of 0.90 and 1.00, respectively.     

Results remained consistent in various sensitivity and subgroup analyses, including limiting the data to just the canagliflozin group. Overall, the fracture rate was greater with female sex, frailty, older age, and insulin use, consistent across drug classes.

The risks for falls and hypoglycemia were lower in the SGLT2 inhibitor versus matched DPP-4 inhibitor groups (hazard ratio, 0.82), and there was no difference in syncope. None of those differences were significant for the SGLT2 inhibitor group compared with the GLP-1 agonist group.

Consistent with previous data, the risk for diabetic ketoacidosis was higher with SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 agonists (HR, 1.29 and 1.58), and the risk for heart failure hospitalization was lower (HR, 0.42 and 0.69).

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, Harvard Medical School. Dr. Zhuo was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does not appear to raise the risk for fractures in older adults, new research suggests.

The data come from a nationwide propensity score-matched study of U.S. Medicare recipients with type 2 diabetes who were new users of either an SGLT2 inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors was not associated with an increased risk of nontraumatic fractures compared with DPP-4 inhibitors or GLP-1 agonists. Results were consistent across categories of sex, frailty, age, and insulin use,” say Min Zhuo, MD, of Harvard Medical School, Boston, and colleagues, who published their work online October 27 in JAMA Network Open.

“Our results add to the evidence base evaluating the safety profile of SGLT2 inhibitors in older adults outside of [randomized controlled trials] and further characterize the risk-benefit balance of SGLT2 inhibitors in clinical practice,” they write.

Asked to comment, Simeon I. Taylor, MD, PhD, told this news organization, “This is a high-quality study that is generally reassuring that relatively short, less than 1 year, treatment with an SGLT2 inhibitor does not appear to significantly increase the risk of bone fractures.”

However, Dr. Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, also noted: “Notwithstanding these reassuring data, the paper also does a good job of pointing out important limitations.”

“Most importantly, these data do not address questions related to the risk of long-term chronic therapy. It is instructive to refer back to the published data demonstrating an approximately 2-year lag before a significant increase in the risk of fracture was observed in rosiglitazone-treated patients in the ADOPT study. The length of the lag is likely related to the baseline bone mineral density at the time drug therapy is initiated. These considerations may contribute to the observed variation in bone-related outcomes in different studies.”

Concern about SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS study, in which the overall fracture risk with canagliflozin was a significant 26% higher than placebo. However, subsequent larger randomized trials of canagliflozin and other SGLT2 inhibitors did not find the same risk.

In addition, previous observational studies in younger adults have also not found use of SGLT2 inhibitors to be associated with increased fracture risk compared with DPP-4 inhibitors or GLP-1 agonists.
 

Understanding fracture risk with SGLT2 inhibitors is ‘critical’

Older adults with type 2 diabetes may benefit from reductions in atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death associated with SGLT2 inhibitors, but the fact that aging may have negative effects on bone metabolism means “understanding the fracture risk associated with SGLT2 inhibitors in older adults with type 2 diabetes is critical,” say Dr. Zhuo and colleagues.

In the current study, they analyzed claims data for Medicare beneficiaries aged 66 years and older (1 year past Medicare eligibility) who were newly prescribed an SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1 agonist between April 1, 2013 and Dec. 31, 2017.

A total of 45,889 patients from each treatment group were propensity-matched using 58 baseline characteristics, for a total of 137,667 patients.

After matching, there were 501 events of the primary composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By treatment group, fracture rates per 1,000 person-years were 4.69, 5.26, and 4.71 for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists respectively.

The differences between patients taking DPP-4 inhibitors or GLP-1 agonists compared with SGLT2 inhibitors were not significant, with hazard ratios of 0.90 and 1.00, respectively.     

Results remained consistent in various sensitivity and subgroup analyses, including limiting the data to just the canagliflozin group. Overall, the fracture rate was greater with female sex, frailty, older age, and insulin use, consistent across drug classes.

The risks for falls and hypoglycemia were lower in the SGLT2 inhibitor versus matched DPP-4 inhibitor groups (hazard ratio, 0.82), and there was no difference in syncope. None of those differences were significant for the SGLT2 inhibitor group compared with the GLP-1 agonist group.

Consistent with previous data, the risk for diabetic ketoacidosis was higher with SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 agonists (HR, 1.29 and 1.58), and the risk for heart failure hospitalization was lower (HR, 0.42 and 0.69).

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, Harvard Medical School. Dr. Zhuo was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does not appear to raise the risk for fractures in older adults, new research suggests.

The data come from a nationwide propensity score-matched study of U.S. Medicare recipients with type 2 diabetes who were new users of either an SGLT2 inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors was not associated with an increased risk of nontraumatic fractures compared with DPP-4 inhibitors or GLP-1 agonists. Results were consistent across categories of sex, frailty, age, and insulin use,” say Min Zhuo, MD, of Harvard Medical School, Boston, and colleagues, who published their work online October 27 in JAMA Network Open.

“Our results add to the evidence base evaluating the safety profile of SGLT2 inhibitors in older adults outside of [randomized controlled trials] and further characterize the risk-benefit balance of SGLT2 inhibitors in clinical practice,” they write.

Asked to comment, Simeon I. Taylor, MD, PhD, told this news organization, “This is a high-quality study that is generally reassuring that relatively short, less than 1 year, treatment with an SGLT2 inhibitor does not appear to significantly increase the risk of bone fractures.”

However, Dr. Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, also noted: “Notwithstanding these reassuring data, the paper also does a good job of pointing out important limitations.”

“Most importantly, these data do not address questions related to the risk of long-term chronic therapy. It is instructive to refer back to the published data demonstrating an approximately 2-year lag before a significant increase in the risk of fracture was observed in rosiglitazone-treated patients in the ADOPT study. The length of the lag is likely related to the baseline bone mineral density at the time drug therapy is initiated. These considerations may contribute to the observed variation in bone-related outcomes in different studies.”

Concern about SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS study, in which the overall fracture risk with canagliflozin was a significant 26% higher than placebo. However, subsequent larger randomized trials of canagliflozin and other SGLT2 inhibitors did not find the same risk.

In addition, previous observational studies in younger adults have also not found use of SGLT2 inhibitors to be associated with increased fracture risk compared with DPP-4 inhibitors or GLP-1 agonists.
 

Understanding fracture risk with SGLT2 inhibitors is ‘critical’

Older adults with type 2 diabetes may benefit from reductions in atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death associated with SGLT2 inhibitors, but the fact that aging may have negative effects on bone metabolism means “understanding the fracture risk associated with SGLT2 inhibitors in older adults with type 2 diabetes is critical,” say Dr. Zhuo and colleagues.

In the current study, they analyzed claims data for Medicare beneficiaries aged 66 years and older (1 year past Medicare eligibility) who were newly prescribed an SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1 agonist between April 1, 2013 and Dec. 31, 2017.

A total of 45,889 patients from each treatment group were propensity-matched using 58 baseline characteristics, for a total of 137,667 patients.

After matching, there were 501 events of the primary composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By treatment group, fracture rates per 1,000 person-years were 4.69, 5.26, and 4.71 for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists respectively.

The differences between patients taking DPP-4 inhibitors or GLP-1 agonists compared with SGLT2 inhibitors were not significant, with hazard ratios of 0.90 and 1.00, respectively.     

Results remained consistent in various sensitivity and subgroup analyses, including limiting the data to just the canagliflozin group. Overall, the fracture rate was greater with female sex, frailty, older age, and insulin use, consistent across drug classes.

The risks for falls and hypoglycemia were lower in the SGLT2 inhibitor versus matched DPP-4 inhibitor groups (hazard ratio, 0.82), and there was no difference in syncope. None of those differences were significant for the SGLT2 inhibitor group compared with the GLP-1 agonist group.

Consistent with previous data, the risk for diabetic ketoacidosis was higher with SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 agonists (HR, 1.29 and 1.58), and the risk for heart failure hospitalization was lower (HR, 0.42 and 0.69).

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, Harvard Medical School. Dr. Zhuo was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

“Short-term hospitalization [for reasons other than diabetes] may not be the time to intervene in long-term diabetes management,” researchers conclude.

They found that, in a national cohort of older almost entirely male veterans with non–insulin-treated type 2 diabetes who were hospitalized for non–diabetes-related common medical conditions, intensified diabetes treatment on hospital discharge was linked to an increased risk of severe hypoglycemia in the immediate postdischarge period.

However, diabetes treatment intensification – that is, receiving a prescription for a new or higher dose of diabetes medicine – was not associated with decreased risks of severe hyperglycemia or with improved glycemic (hemoglobin A1c) control at 30 days or 1 year, according to study results, published in JAMA Network Open.

“We didn’t see a reduction in diabetes emergencies in more intensively treated patients,” lead investigator Timothy S. Anderson, MD, said in an interview.

Also, importantly, there was a low rate of persistence with the new treatment. “Half of the patients were no longer taking these [intensified diabetes medicines] at 1 year, which tells me that context is key,” he pointed out. “If a patient is in the hospital for diabetes [unlike the patients in this study], I think it makes a lot of sense to modify and adjust their regimen to try to help them right then and there.”

The overall risk of severe hyperglycemia or severe hypoglycemia was pretty small in the overall cohort, Dr. Anderson noted, “but we do put people at risk of leaving the hospital and ending up back in the hospital with low blood sugar when we intensify medications, and there’s not necessarily a good signal to suggest that it’s all that urgent to change these medicines.”

Instead, the “safer path” may be to make recommendations to the patient’s outpatient physician and also inform the patient – for example, “We saw some concerns about your diabetes while you were in the hospital, and this is really something that should be looked at when you’re recovered and feeling better from the rest of your health standpoint” – rather than making a diabetes medication change while the person is acutely ill or recovering from illness, said Dr. Anderson, from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.

The researchers also found an “unexpected” significant decrease in 30-day mortality in the patients with intensified diabetes treatment, which was probably because of confounding that was not accounted for, Dr. Anderson speculated, since clinical trials have consistently shown that benefits from diabetes medications take a longer time to show an effect.
 

‘Important study,’ but lacked newer meds

This is an “important” study for primary care and in-hospital physicians that shows that “hospitalization is really not the time and the place” to intensify diabetes medication, Rozalina G. McCoy, MD, coauthor of an invited commentary, told this news organization in an interview.

“While overcoming treatment inertia is important, [it should be] done appropriately, so that we don’t overtreat patients,” Dr. McCoy, of the Mayo Clinic in Rochester, Minn., stressed.

The very low rate of persistence of taking intensified medications is a major finding, she agreed. Hospitalized patients “are not in their usual state of health, so if we make long-term treatment decisions based on their acute abnormal situation, that may not be appropriate.”

However, patients with high A1c may benefit from a change at hospital discharge rather than when they see their primary care provider, with the caveat that they need close follow-up as an outpatient.

The study emphasizes the “need for longitudinal patient care rather than episodic patches,” according to Dr. McCoy.

For example, a patient who is hospitalized for a chronic obstructive pulmonary disease or asthma exacerbation may be receiving steroids that cause high blood glucose levels but as soon as they’re done with their steroid course, blood glucose will decrease, so the “need for close outpatient follow-up is very important.”

One limitation of the current work is that an earlier study in the same population by the research group showed that 49% of patients whose treatment regimens were intensified had limited life expectancy or were at or below their A1c goal, so they would not have benefited from the stepped-up treatment, she noted.

Another limitation is that the findings cannot be generalized to women or younger patients, or to patients treated with glucagonlike peptide 1 (GLP-1)–receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors.

The study patients were seen in the U.S. Veterans Health Administration health system when these newer agents were not used. Three-quarters of patients received intensified treatment with sulfonylurea or insulin, and only one patient received a new GLP-1–receptor agonist.

Ideally, Dr. McCoy said, patients should have been prescribed a GLP-1–receptor agonist if they had atherosclerotic cardiovascular disease or kidney disease, or an SGLT2 inhibitor if they had kidney disease or heart failure, which may have led to different results, and would need to be determined in further study.

Dr. Anderson agreed that “SGLT2 inhibitors and GLP1 agonists are broadly much safer than the older diabetes medicines, at least when it comes to risk of hypoglycemia, and may have more clear benefits in heart disease and mortality. So I would not want to extrapolate our findings to those new classes,” he said. “A similar set of studies would need to be done.”
 

Study rationale and findings

Hospitalized older adults with diabetes commonly have transiently elevated blood glucose levels that might lead clinicians to discharge them from hospital with a prescription for more intensive diabetes medications than they were on before they were hospitalized, but it is not clear if these diabetes medication changes would improve outcomes.

To investigate this, the researchers analyzed data from patients with diabetes who were 65 and older and hospitalized for common medical conditions in VHA hospitals during January 2011–September 2016, and then discharged to the community.

They excluded patients who were hospitalized for things that require immediate change in diabetes treatment and patients who were using insulin before their hospitalization (because instructions to modify insulin dosing frequently don’t have a new prescription).

The researchers identified 28,198 adults with diabetes who were not on insulin and were hospitalized in the VHA health system for heart failure (18%), coronary artery disease (13%), chronic obstructive pulmonary disease (10%), pneumonia (9.6%), and urinary tract infection (7.5%), and less often and not in decreasing order, for acute coronary syndrome, arrhythmia, asthma, chest pain, conduction disorders, heart valve disorders, sepsis, skin infection, stroke, and transient ischemic attack.

Of these patients, 2,768 patients (9.8%) received diabetes medication intensification, and the researchers matched 2,648 of these patients with an equal number of patients who did not receive this treatment intensification.

The patients in each group had a mean age of 73 and 98.5% were male; 78% were White.

They had a mean A1c of 7.9%. Most were receiving sulfonylurea (43%) or metformin (39%), and few were receiving thiazolidinediones (4.1%), alpha-glucosidase inhibitors (2.7%), dipeptidyl peptidase 4 inhibitors (2.0%), or other types of diabetes drugs (0.1%).

Of the 2,768 patients who received intensified diabetes medication, most received a prescription for insulin (51%) or sulfonylurea (23%).

In the propensity-matched cohort, patients with intensified diabetes medication had a higher rate of severe hypoglycemia at 30 days (1% vs. 0.5%), which translated into a significant twofold higher risk (hazard ratio, 2.17).

The rates of severe hypoglycemia at 1 year were similar in both groups (3.1% and 2.9%).

The incidence of severe hyperglycemia was the same in both groups at 30 days (0.3%) and 1 year (1.3%).

In secondary outcomes, at 1 year, 48% of new oral diabetes medications and 39% of new insulin prescriptions were no longer being filled.

Overall, patients who were discharged with intensified diabetes medication were significantly less likely to die within 30 days than the other patients (1.3% vs. 2.4%; HR, 0.55).

However, this mortality benefit was found only in the subgroup of 2,524 patients who had uncontrolled diabetes when they were admitted to hospital (A1c >7.5%; mean A1c, 9.1%), and not in the propensity-matched subgroup of 2,672 patients who had controlled diabetes then (A1c up to 7.5%; mean A1c, 6.8%).

There was no significant difference in 1-year mortality in patients with versus without intensified treatment (15.8% vs. 17.8%).

There were also no significant between-group difference in rates of hospital readmission at 30 days (roughly 17%) or 1 year (roughly 51%).

The decreases in mean A1c from hospital discharge to 1 year later were also the same in both groups (going from 7.9% to 7.7%).

The study was funded by grants from the National Institute on Aging and the American College of Cardiology. Dr. Anderson has no relevant financial disclosures. Dr. McCoy reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases, AARP, and the Patient-Centered Outcomes Research Institute outside the submitted work. The disclosures of the other authors and the editorial coauthor are available with the article and commentary.

“Short-term hospitalization [for reasons other than diabetes] may not be the time to intervene in long-term diabetes management,” researchers conclude.

They found that, in a national cohort of older almost entirely male veterans with non–insulin-treated type 2 diabetes who were hospitalized for non–diabetes-related common medical conditions, intensified diabetes treatment on hospital discharge was linked to an increased risk of severe hypoglycemia in the immediate postdischarge period.

However, diabetes treatment intensification – that is, receiving a prescription for a new or higher dose of diabetes medicine – was not associated with decreased risks of severe hyperglycemia or with improved glycemic (hemoglobin A1c) control at 30 days or 1 year, according to study results, published in JAMA Network Open.

“We didn’t see a reduction in diabetes emergencies in more intensively treated patients,” lead investigator Timothy S. Anderson, MD, said in an interview.

Also, importantly, there was a low rate of persistence with the new treatment. “Half of the patients were no longer taking these [intensified diabetes medicines] at 1 year, which tells me that context is key,” he pointed out. “If a patient is in the hospital for diabetes [unlike the patients in this study], I think it makes a lot of sense to modify and adjust their regimen to try to help them right then and there.”

The overall risk of severe hyperglycemia or severe hypoglycemia was pretty small in the overall cohort, Dr. Anderson noted, “but we do put people at risk of leaving the hospital and ending up back in the hospital with low blood sugar when we intensify medications, and there’s not necessarily a good signal to suggest that it’s all that urgent to change these medicines.”

Instead, the “safer path” may be to make recommendations to the patient’s outpatient physician and also inform the patient – for example, “We saw some concerns about your diabetes while you were in the hospital, and this is really something that should be looked at when you’re recovered and feeling better from the rest of your health standpoint” – rather than making a diabetes medication change while the person is acutely ill or recovering from illness, said Dr. Anderson, from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.

The researchers also found an “unexpected” significant decrease in 30-day mortality in the patients with intensified diabetes treatment, which was probably because of confounding that was not accounted for, Dr. Anderson speculated, since clinical trials have consistently shown that benefits from diabetes medications take a longer time to show an effect.
 

‘Important study,’ but lacked newer meds

This is an “important” study for primary care and in-hospital physicians that shows that “hospitalization is really not the time and the place” to intensify diabetes medication, Rozalina G. McCoy, MD, coauthor of an invited commentary, told this news organization in an interview.

“While overcoming treatment inertia is important, [it should be] done appropriately, so that we don’t overtreat patients,” Dr. McCoy, of the Mayo Clinic in Rochester, Minn., stressed.

The very low rate of persistence of taking intensified medications is a major finding, she agreed. Hospitalized patients “are not in their usual state of health, so if we make long-term treatment decisions based on their acute abnormal situation, that may not be appropriate.”

However, patients with high A1c may benefit from a change at hospital discharge rather than when they see their primary care provider, with the caveat that they need close follow-up as an outpatient.

The study emphasizes the “need for longitudinal patient care rather than episodic patches,” according to Dr. McCoy.

For example, a patient who is hospitalized for a chronic obstructive pulmonary disease or asthma exacerbation may be receiving steroids that cause high blood glucose levels but as soon as they’re done with their steroid course, blood glucose will decrease, so the “need for close outpatient follow-up is very important.”

One limitation of the current work is that an earlier study in the same population by the research group showed that 49% of patients whose treatment regimens were intensified had limited life expectancy or were at or below their A1c goal, so they would not have benefited from the stepped-up treatment, she noted.

Another limitation is that the findings cannot be generalized to women or younger patients, or to patients treated with glucagonlike peptide 1 (GLP-1)–receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors.

The study patients were seen in the U.S. Veterans Health Administration health system when these newer agents were not used. Three-quarters of patients received intensified treatment with sulfonylurea or insulin, and only one patient received a new GLP-1–receptor agonist.

Ideally, Dr. McCoy said, patients should have been prescribed a GLP-1–receptor agonist if they had atherosclerotic cardiovascular disease or kidney disease, or an SGLT2 inhibitor if they had kidney disease or heart failure, which may have led to different results, and would need to be determined in further study.

Dr. Anderson agreed that “SGLT2 inhibitors and GLP1 agonists are broadly much safer than the older diabetes medicines, at least when it comes to risk of hypoglycemia, and may have more clear benefits in heart disease and mortality. So I would not want to extrapolate our findings to those new classes,” he said. “A similar set of studies would need to be done.”
 

Study rationale and findings

Hospitalized older adults with diabetes commonly have transiently elevated blood glucose levels that might lead clinicians to discharge them from hospital with a prescription for more intensive diabetes medications than they were on before they were hospitalized, but it is not clear if these diabetes medication changes would improve outcomes.

To investigate this, the researchers analyzed data from patients with diabetes who were 65 and older and hospitalized for common medical conditions in VHA hospitals during January 2011–September 2016, and then discharged to the community.

They excluded patients who were hospitalized for things that require immediate change in diabetes treatment and patients who were using insulin before their hospitalization (because instructions to modify insulin dosing frequently don’t have a new prescription).

The researchers identified 28,198 adults with diabetes who were not on insulin and were hospitalized in the VHA health system for heart failure (18%), coronary artery disease (13%), chronic obstructive pulmonary disease (10%), pneumonia (9.6%), and urinary tract infection (7.5%), and less often and not in decreasing order, for acute coronary syndrome, arrhythmia, asthma, chest pain, conduction disorders, heart valve disorders, sepsis, skin infection, stroke, and transient ischemic attack.

Of these patients, 2,768 patients (9.8%) received diabetes medication intensification, and the researchers matched 2,648 of these patients with an equal number of patients who did not receive this treatment intensification.

The patients in each group had a mean age of 73 and 98.5% were male; 78% were White.

They had a mean A1c of 7.9%. Most were receiving sulfonylurea (43%) or metformin (39%), and few were receiving thiazolidinediones (4.1%), alpha-glucosidase inhibitors (2.7%), dipeptidyl peptidase 4 inhibitors (2.0%), or other types of diabetes drugs (0.1%).

Of the 2,768 patients who received intensified diabetes medication, most received a prescription for insulin (51%) or sulfonylurea (23%).

In the propensity-matched cohort, patients with intensified diabetes medication had a higher rate of severe hypoglycemia at 30 days (1% vs. 0.5%), which translated into a significant twofold higher risk (hazard ratio, 2.17).

The rates of severe hypoglycemia at 1 year were similar in both groups (3.1% and 2.9%).

The incidence of severe hyperglycemia was the same in both groups at 30 days (0.3%) and 1 year (1.3%).

In secondary outcomes, at 1 year, 48% of new oral diabetes medications and 39% of new insulin prescriptions were no longer being filled.

Overall, patients who were discharged with intensified diabetes medication were significantly less likely to die within 30 days than the other patients (1.3% vs. 2.4%; HR, 0.55).

However, this mortality benefit was found only in the subgroup of 2,524 patients who had uncontrolled diabetes when they were admitted to hospital (A1c >7.5%; mean A1c, 9.1%), and not in the propensity-matched subgroup of 2,672 patients who had controlled diabetes then (A1c up to 7.5%; mean A1c, 6.8%).

There was no significant difference in 1-year mortality in patients with versus without intensified treatment (15.8% vs. 17.8%).

There were also no significant between-group difference in rates of hospital readmission at 30 days (roughly 17%) or 1 year (roughly 51%).

The decreases in mean A1c from hospital discharge to 1 year later were also the same in both groups (going from 7.9% to 7.7%).

The study was funded by grants from the National Institute on Aging and the American College of Cardiology. Dr. Anderson has no relevant financial disclosures. Dr. McCoy reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases, AARP, and the Patient-Centered Outcomes Research Institute outside the submitted work. The disclosures of the other authors and the editorial coauthor are available with the article and commentary.

“Short-term hospitalization [for reasons other than diabetes] may not be the time to intervene in long-term diabetes management,” researchers conclude.

They found that, in a national cohort of older almost entirely male veterans with non–insulin-treated type 2 diabetes who were hospitalized for non–diabetes-related common medical conditions, intensified diabetes treatment on hospital discharge was linked to an increased risk of severe hypoglycemia in the immediate postdischarge period.

However, diabetes treatment intensification – that is, receiving a prescription for a new or higher dose of diabetes medicine – was not associated with decreased risks of severe hyperglycemia or with improved glycemic (hemoglobin A1c) control at 30 days or 1 year, according to study results, published in JAMA Network Open.

“We didn’t see a reduction in diabetes emergencies in more intensively treated patients,” lead investigator Timothy S. Anderson, MD, said in an interview.

Also, importantly, there was a low rate of persistence with the new treatment. “Half of the patients were no longer taking these [intensified diabetes medicines] at 1 year, which tells me that context is key,” he pointed out. “If a patient is in the hospital for diabetes [unlike the patients in this study], I think it makes a lot of sense to modify and adjust their regimen to try to help them right then and there.”

The overall risk of severe hyperglycemia or severe hypoglycemia was pretty small in the overall cohort, Dr. Anderson noted, “but we do put people at risk of leaving the hospital and ending up back in the hospital with low blood sugar when we intensify medications, and there’s not necessarily a good signal to suggest that it’s all that urgent to change these medicines.”

Instead, the “safer path” may be to make recommendations to the patient’s outpatient physician and also inform the patient – for example, “We saw some concerns about your diabetes while you were in the hospital, and this is really something that should be looked at when you’re recovered and feeling better from the rest of your health standpoint” – rather than making a diabetes medication change while the person is acutely ill or recovering from illness, said Dr. Anderson, from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.

The researchers also found an “unexpected” significant decrease in 30-day mortality in the patients with intensified diabetes treatment, which was probably because of confounding that was not accounted for, Dr. Anderson speculated, since clinical trials have consistently shown that benefits from diabetes medications take a longer time to show an effect.
 

‘Important study,’ but lacked newer meds

This is an “important” study for primary care and in-hospital physicians that shows that “hospitalization is really not the time and the place” to intensify diabetes medication, Rozalina G. McCoy, MD, coauthor of an invited commentary, told this news organization in an interview.

“While overcoming treatment inertia is important, [it should be] done appropriately, so that we don’t overtreat patients,” Dr. McCoy, of the Mayo Clinic in Rochester, Minn., stressed.

The very low rate of persistence of taking intensified medications is a major finding, she agreed. Hospitalized patients “are not in their usual state of health, so if we make long-term treatment decisions based on their acute abnormal situation, that may not be appropriate.”

However, patients with high A1c may benefit from a change at hospital discharge rather than when they see their primary care provider, with the caveat that they need close follow-up as an outpatient.

The study emphasizes the “need for longitudinal patient care rather than episodic patches,” according to Dr. McCoy.

For example, a patient who is hospitalized for a chronic obstructive pulmonary disease or asthma exacerbation may be receiving steroids that cause high blood glucose levels but as soon as they’re done with their steroid course, blood glucose will decrease, so the “need for close outpatient follow-up is very important.”

One limitation of the current work is that an earlier study in the same population by the research group showed that 49% of patients whose treatment regimens were intensified had limited life expectancy or were at or below their A1c goal, so they would not have benefited from the stepped-up treatment, she noted.

Another limitation is that the findings cannot be generalized to women or younger patients, or to patients treated with glucagonlike peptide 1 (GLP-1)–receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors.

The study patients were seen in the U.S. Veterans Health Administration health system when these newer agents were not used. Three-quarters of patients received intensified treatment with sulfonylurea or insulin, and only one patient received a new GLP-1–receptor agonist.

Ideally, Dr. McCoy said, patients should have been prescribed a GLP-1–receptor agonist if they had atherosclerotic cardiovascular disease or kidney disease, or an SGLT2 inhibitor if they had kidney disease or heart failure, which may have led to different results, and would need to be determined in further study.

Dr. Anderson agreed that “SGLT2 inhibitors and GLP1 agonists are broadly much safer than the older diabetes medicines, at least when it comes to risk of hypoglycemia, and may have more clear benefits in heart disease and mortality. So I would not want to extrapolate our findings to those new classes,” he said. “A similar set of studies would need to be done.”
 

Study rationale and findings

Hospitalized older adults with diabetes commonly have transiently elevated blood glucose levels that might lead clinicians to discharge them from hospital with a prescription for more intensive diabetes medications than they were on before they were hospitalized, but it is not clear if these diabetes medication changes would improve outcomes.

To investigate this, the researchers analyzed data from patients with diabetes who were 65 and older and hospitalized for common medical conditions in VHA hospitals during January 2011–September 2016, and then discharged to the community.

They excluded patients who were hospitalized for things that require immediate change in diabetes treatment and patients who were using insulin before their hospitalization (because instructions to modify insulin dosing frequently don’t have a new prescription).

The researchers identified 28,198 adults with diabetes who were not on insulin and were hospitalized in the VHA health system for heart failure (18%), coronary artery disease (13%), chronic obstructive pulmonary disease (10%), pneumonia (9.6%), and urinary tract infection (7.5%), and less often and not in decreasing order, for acute coronary syndrome, arrhythmia, asthma, chest pain, conduction disorders, heart valve disorders, sepsis, skin infection, stroke, and transient ischemic attack.

Of these patients, 2,768 patients (9.8%) received diabetes medication intensification, and the researchers matched 2,648 of these patients with an equal number of patients who did not receive this treatment intensification.

The patients in each group had a mean age of 73 and 98.5% were male; 78% were White.

They had a mean A1c of 7.9%. Most were receiving sulfonylurea (43%) or metformin (39%), and few were receiving thiazolidinediones (4.1%), alpha-glucosidase inhibitors (2.7%), dipeptidyl peptidase 4 inhibitors (2.0%), or other types of diabetes drugs (0.1%).

Of the 2,768 patients who received intensified diabetes medication, most received a prescription for insulin (51%) or sulfonylurea (23%).

In the propensity-matched cohort, patients with intensified diabetes medication had a higher rate of severe hypoglycemia at 30 days (1% vs. 0.5%), which translated into a significant twofold higher risk (hazard ratio, 2.17).

The rates of severe hypoglycemia at 1 year were similar in both groups (3.1% and 2.9%).

The incidence of severe hyperglycemia was the same in both groups at 30 days (0.3%) and 1 year (1.3%).

In secondary outcomes, at 1 year, 48% of new oral diabetes medications and 39% of new insulin prescriptions were no longer being filled.

Overall, patients who were discharged with intensified diabetes medication were significantly less likely to die within 30 days than the other patients (1.3% vs. 2.4%; HR, 0.55).

However, this mortality benefit was found only in the subgroup of 2,524 patients who had uncontrolled diabetes when they were admitted to hospital (A1c >7.5%; mean A1c, 9.1%), and not in the propensity-matched subgroup of 2,672 patients who had controlled diabetes then (A1c up to 7.5%; mean A1c, 6.8%).

There was no significant difference in 1-year mortality in patients with versus without intensified treatment (15.8% vs. 17.8%).

There were also no significant between-group difference in rates of hospital readmission at 30 days (roughly 17%) or 1 year (roughly 51%).

The decreases in mean A1c from hospital discharge to 1 year later were also the same in both groups (going from 7.9% to 7.7%).

The study was funded by grants from the National Institute on Aging and the American College of Cardiology. Dr. Anderson has no relevant financial disclosures. Dr. McCoy reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases, AARP, and the Patient-Centered Outcomes Research Institute outside the submitted work. The disclosures of the other authors and the editorial coauthor are available with the article and commentary.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

At Wayne State University’s Stress, Trauma, and Anxiety Research Clinic (STARC) in Michigan, researchers are developing novel interventions for treating some very ancient phobias hardwired into the human brain. By using augmented reality as means of conducting exposure therapy, STARC researchers – including Shantanu Madaboosi, Rakesh Ramaswamy, and Lana Grasser – and STARC director Arash Javanbakht, MD, have produced compelling evidence that they can free patients of their often debilitating fears of spiders, dogs, and snakes. Yet their work doesn’t stop there, and research into treating anxiety and posttraumatic stress disorder among first responders and others with high-stress occupations is ongoing.

This news organization spoke with Dr. Javanbakht, a psychiatrist, about the technological advances that have made this work possible; the future of remote-based psychiatry; and his tarantula colleague, Tony.
 

Augmenting exposure therapy

How did you begin using artificial intelligence as a way of delivering exposure therapy?

Exposure therapy is a very effective treatment for phobias, obsessive-compulsive disorder, and PTSD. But the problem we had is that, if someone comes to me and says they’re afraid of dogs, snakes, or spiders, I don’t have those in my office. Or, if its social phobia, I can’t create those scenarios. So, despite being such an effective treatment, it’s not utilized as much as it should be.

Several years ago, I saw a TED talk by the CEO of an augmented reality company who happened to be a neuroscientist. I thought the concept was amazing, because it offered a way to overcome those limitations.

Mixed augmented reality allows us to bring all those feared objects to the clinic. I can bring my Labrador to the office for someone who’s afraid of dogs, and they can get the exposure to that one dog. But we know good exposure therapy needs to be generalizable, with as many different breeds of dogs as possible, and is context dependent. If the patient sees a dog in their neighborhood, their fear response may come back. Doing it in a real-life context, and offering as many contexts as possible, makes it more effective.

Augmented reality allows all of these options because you can have as many different types of virtual objects as you want, and the difference between augmented reality and virtual reality is that augmented reality happens in a real-life context. You wear the goggles and you can walk around the environment and track the object, so the context is more realistic.
 

When did you begin researching augmented reality as a clinical tool?

I became a faculty member here in 2015, right out of my residency training, and I think it was around 2016 or 2017 that we began this work.

I’m very much involved in exposure therapy, utilize it myself, train others, and research how it works and changes the brain. I knew the ins and outs and what would make a better exposure therapy, based on my knowledge of neuroscience.

We spend time thinking about how we can apply these neuroscientific principles in software that can also be easily used by a not very technologically savvy therapist. Because that has been a big barrier when it comes to technology and human use in medicine.

Initially, we had a company create the software for us, but we’ve since brought all the programming inside.

The cool thing about these augmented reality devices is that they have excellent surface mapping. As soon as the person wears the goggles, it automatically maps the surfaces and provides a 3D view of the patient’s environment on the therapist’s computer. Say you’re treating a patient with a fear of spiders. Through drop-down menus, the therapist can choose what type of spider, its color and size, where it should be placed, and the motion. I can choose to move the spider from 6 feet away on the floor to the walls to the ceiling.
 

Virtual phobias, real fear

A big question for a lot of people was if the spiders are virtual, will they be scary, because it has to be realistic enough to create a fear response for the therapy to work. We use a couple of wires that you can put on a person’s finger and hook them up to a tablet or a cell phone. This provides an online measure of a person’s autonomic sympathetic response.

Like a lie detector test?

Exactly. We put that on their fingers and exposed them to a real-life tarantula and to our virtual tarantulas, and the fear response was no different. That means these do create an objective fear reaction in the body.

We also had people who said, “I know this is not real. I won’t be scared.” And when we started the therapy, it was with a tiny spider 5 meters away from them, and they’d lift their legs off the floor.

With the treatment, we’d come to one room and start with a very little spider, far from them. Then gradually we move them up to bigger, more diverse types of spiders, which are moving around. The patient comes near and tries to touch them.

Then at some point, I’d put a spiderweb on the door, put a few spiders on that, open the door, and have the patient walk through it. They kept walking through this spiderweb.

When they were desensitized to these spiders in this context – and as I said, context is important – we’d go to another room. This was darker, more like a basement, and we’d continue the same thing. That would actually take much less time because they already had desensitized a lot.

In our field, sense of control is very important, especially for when a patient goes home. So at the end, I’d leave the room and talk to the patient via a baby monitor. The patient was surrounded by 20 tarantulas, without the prompt moving around the environment.

Now that they’re desensitized to my virtual spiders, the question is, how would that apply to a real spider? So, we had a real live tarantula, whose name was Tony Stark, because we’re the STARC lab. We’d put Tony at the end of a long hallway before the treatment and see how close the patients could get to him.

Everybody who got the treatment was able to touch the tank containing the tarantula. It was only one treatment session; nobody’s was longer than 1 hour, and the average treatment time was 38 minutes.
 

That’s pretty effective.

It’s pretty good, compared with other studies. And I believe this is because of all the components I mentioned: being able to use your real environment; combining it with the real tarantula; the variety of the types of the feared objects; and, of course, giving the patient a sense of autonomy at the end.

Then we had to see how prolonged the effects are. We had them come in 1 week and 1 month after the treatment. I’d remind them of the principles of good exposure therapy and ask them to keep practicing at home between the sessions, looking at pictures and videos. But we never tested who did or did not do it.

After 1 week and 1 month, the effects were either the same or better. A larger number of people at 1 month were able to touch the tarantula than right after treatment.
 

Treating PTSD in first responders

Did you start with spiders and dogs because those are common fears?

We started with spiders because that worked with the initial goal of creating a prototype. Spiders’ behavior is simple enough for the programming, which takes a lot of time. Another reason for choosing spiders was that we had a lot of other studies of real and virtual reality exposure therapy to compare against.

I think another reason for our success is that, when you do real exposure therapy, you have just one scared tarantula in the corner of their tank, and they don’t listen to you. But my spiders listen to me and do exactly what I tell them.

After our initial success, we obtained more funds to expand it to other phobias. The cool thing is that we don’t need separate software for different phobias. You can choose dogs or snakes, add it to the person’s environment, and decide their behaviors.

We just started a clinical trial using dogs, and another group in Turkey is running a clinical trial with dogs. Eastern Michigan University is working with spiders. And a clinic at the University of Nebraska Medical Center is going to start using them in real-world clinics, not for research.

We have another project whose goal is helping reduce the impact of trauma and also treating PTSD in first responders, who are exposed to a lot of horrible things. Rates of PTSD are around 20%-30% among cops, firefighters, and EMS personnel.

They commonly find it very painful being in crowds because the fight-or-flight instinct in the brain is constantly screening for any sign of threat in their environment. We’re working on them walking into an empty room wearing the goggles, and then their therapist can scale the stimulus up and down.

There’ll be two people in front of you talking to each other, and then another group comes in, and people get louder. People can look at you and talk to you. There’s kids running, Fourth of July fireworks, and other things that might bother someone who’s been involved in gun- or explosion-related traumas. You gradually scale up when the person is next to their therapist.

Another thing we’re doing is related to cardiopulmonary resuscitation. If a young person dies in a CPR situation, that is really painful and traumatic. So, for exposure therapy to that, we’re creating a difficult CPR scenario when that person may die. The responder wears the goggles and basically watches a group of people doing CPR while standing next to a therapist who can help them navigate it and then scale it off.

Another goal is combining this with telemedicine, where the person can do it in their real-life environment. Imagine a person with military trauma. You can put them back in the barracks, connected with their psychiatrists via telemedicine. Then we would put humans in military fatigues near them and have them interact with them to feel comfortable with that situation.
 

What else is next for you and your group?

The next biggest challenge that we’re tackling is PTSD, because of course creating human-encounter scenarios is much more complicated than spiders and dogs. We’re in the midst of developing this so we can basically bring it to people’s homes.

We’ve been working with some military personnel to see if we can basically give a device to a veteran with PTSD, so they can go home and practice on their own.

There’s another possibility for training. Let’s take the example of a police force, which can have a lot of difficulties and mistakes because of lack of exposure and training. They can wear these goggles, get fully geared up, and be placed in encounters with people of different backgrounds, of different severity, with people who could be severely mentally ill or present different challenges for the officers.

Those situations can teach them a lot. I’m the creator of this thing, but even I’m often surprised by how realistic this technology can be. I find myself interacting with avatars the same way I would if they were real humans. I actually had one of my colleagues, when we started launching the programming with the dogs, immediately jump back. It’s just like the animal brain reacts to them.
 

Last question: Do you actually interact with Tony, the tarantula?

Oh, Tony is my friend. Unfortunately, he’s not with our lab at this moment. He’s on a sabbatical at Eastern Michigan University for their clinical trials. But yes, I’ve held him. He’s very friendly.

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

At Wayne State University’s Stress, Trauma, and Anxiety Research Clinic (STARC) in Michigan, researchers are developing novel interventions for treating some very ancient phobias hardwired into the human brain. By using augmented reality as means of conducting exposure therapy, STARC researchers – including Shantanu Madaboosi, Rakesh Ramaswamy, and Lana Grasser – and STARC director Arash Javanbakht, MD, have produced compelling evidence that they can free patients of their often debilitating fears of spiders, dogs, and snakes. Yet their work doesn’t stop there, and research into treating anxiety and posttraumatic stress disorder among first responders and others with high-stress occupations is ongoing.

This news organization spoke with Dr. Javanbakht, a psychiatrist, about the technological advances that have made this work possible; the future of remote-based psychiatry; and his tarantula colleague, Tony.
 

Augmenting exposure therapy

How did you begin using artificial intelligence as a way of delivering exposure therapy?

Exposure therapy is a very effective treatment for phobias, obsessive-compulsive disorder, and PTSD. But the problem we had is that, if someone comes to me and says they’re afraid of dogs, snakes, or spiders, I don’t have those in my office. Or, if its social phobia, I can’t create those scenarios. So, despite being such an effective treatment, it’s not utilized as much as it should be.

Several years ago, I saw a TED talk by the CEO of an augmented reality company who happened to be a neuroscientist. I thought the concept was amazing, because it offered a way to overcome those limitations.

Mixed augmented reality allows us to bring all those feared objects to the clinic. I can bring my Labrador to the office for someone who’s afraid of dogs, and they can get the exposure to that one dog. But we know good exposure therapy needs to be generalizable, with as many different breeds of dogs as possible, and is context dependent. If the patient sees a dog in their neighborhood, their fear response may come back. Doing it in a real-life context, and offering as many contexts as possible, makes it more effective.

Augmented reality allows all of these options because you can have as many different types of virtual objects as you want, and the difference between augmented reality and virtual reality is that augmented reality happens in a real-life context. You wear the goggles and you can walk around the environment and track the object, so the context is more realistic.
 

When did you begin researching augmented reality as a clinical tool?

I became a faculty member here in 2015, right out of my residency training, and I think it was around 2016 or 2017 that we began this work.

I’m very much involved in exposure therapy, utilize it myself, train others, and research how it works and changes the brain. I knew the ins and outs and what would make a better exposure therapy, based on my knowledge of neuroscience.

We spend time thinking about how we can apply these neuroscientific principles in software that can also be easily used by a not very technologically savvy therapist. Because that has been a big barrier when it comes to technology and human use in medicine.

Initially, we had a company create the software for us, but we’ve since brought all the programming inside.

The cool thing about these augmented reality devices is that they have excellent surface mapping. As soon as the person wears the goggles, it automatically maps the surfaces and provides a 3D view of the patient’s environment on the therapist’s computer. Say you’re treating a patient with a fear of spiders. Through drop-down menus, the therapist can choose what type of spider, its color and size, where it should be placed, and the motion. I can choose to move the spider from 6 feet away on the floor to the walls to the ceiling.
 

Virtual phobias, real fear

A big question for a lot of people was if the spiders are virtual, will they be scary, because it has to be realistic enough to create a fear response for the therapy to work. We use a couple of wires that you can put on a person’s finger and hook them up to a tablet or a cell phone. This provides an online measure of a person’s autonomic sympathetic response.

Like a lie detector test?

Exactly. We put that on their fingers and exposed them to a real-life tarantula and to our virtual tarantulas, and the fear response was no different. That means these do create an objective fear reaction in the body.

We also had people who said, “I know this is not real. I won’t be scared.” And when we started the therapy, it was with a tiny spider 5 meters away from them, and they’d lift their legs off the floor.

With the treatment, we’d come to one room and start with a very little spider, far from them. Then gradually we move them up to bigger, more diverse types of spiders, which are moving around. The patient comes near and tries to touch them.

Then at some point, I’d put a spiderweb on the door, put a few spiders on that, open the door, and have the patient walk through it. They kept walking through this spiderweb.

When they were desensitized to these spiders in this context – and as I said, context is important – we’d go to another room. This was darker, more like a basement, and we’d continue the same thing. That would actually take much less time because they already had desensitized a lot.

In our field, sense of control is very important, especially for when a patient goes home. So at the end, I’d leave the room and talk to the patient via a baby monitor. The patient was surrounded by 20 tarantulas, without the prompt moving around the environment.

Now that they’re desensitized to my virtual spiders, the question is, how would that apply to a real spider? So, we had a real live tarantula, whose name was Tony Stark, because we’re the STARC lab. We’d put Tony at the end of a long hallway before the treatment and see how close the patients could get to him.

Everybody who got the treatment was able to touch the tank containing the tarantula. It was only one treatment session; nobody’s was longer than 1 hour, and the average treatment time was 38 minutes.
 

That’s pretty effective.

It’s pretty good, compared with other studies. And I believe this is because of all the components I mentioned: being able to use your real environment; combining it with the real tarantula; the variety of the types of the feared objects; and, of course, giving the patient a sense of autonomy at the end.

Then we had to see how prolonged the effects are. We had them come in 1 week and 1 month after the treatment. I’d remind them of the principles of good exposure therapy and ask them to keep practicing at home between the sessions, looking at pictures and videos. But we never tested who did or did not do it.

After 1 week and 1 month, the effects were either the same or better. A larger number of people at 1 month were able to touch the tarantula than right after treatment.
 

Treating PTSD in first responders

Did you start with spiders and dogs because those are common fears?

We started with spiders because that worked with the initial goal of creating a prototype. Spiders’ behavior is simple enough for the programming, which takes a lot of time. Another reason for choosing spiders was that we had a lot of other studies of real and virtual reality exposure therapy to compare against.

I think another reason for our success is that, when you do real exposure therapy, you have just one scared tarantula in the corner of their tank, and they don’t listen to you. But my spiders listen to me and do exactly what I tell them.

After our initial success, we obtained more funds to expand it to other phobias. The cool thing is that we don’t need separate software for different phobias. You can choose dogs or snakes, add it to the person’s environment, and decide their behaviors.

We just started a clinical trial using dogs, and another group in Turkey is running a clinical trial with dogs. Eastern Michigan University is working with spiders. And a clinic at the University of Nebraska Medical Center is going to start using them in real-world clinics, not for research.

We have another project whose goal is helping reduce the impact of trauma and also treating PTSD in first responders, who are exposed to a lot of horrible things. Rates of PTSD are around 20%-30% among cops, firefighters, and EMS personnel.

They commonly find it very painful being in crowds because the fight-or-flight instinct in the brain is constantly screening for any sign of threat in their environment. We’re working on them walking into an empty room wearing the goggles, and then their therapist can scale the stimulus up and down.

There’ll be two people in front of you talking to each other, and then another group comes in, and people get louder. People can look at you and talk to you. There’s kids running, Fourth of July fireworks, and other things that might bother someone who’s been involved in gun- or explosion-related traumas. You gradually scale up when the person is next to their therapist.

Another thing we’re doing is related to cardiopulmonary resuscitation. If a young person dies in a CPR situation, that is really painful and traumatic. So, for exposure therapy to that, we’re creating a difficult CPR scenario when that person may die. The responder wears the goggles and basically watches a group of people doing CPR while standing next to a therapist who can help them navigate it and then scale it off.

Another goal is combining this with telemedicine, where the person can do it in their real-life environment. Imagine a person with military trauma. You can put them back in the barracks, connected with their psychiatrists via telemedicine. Then we would put humans in military fatigues near them and have them interact with them to feel comfortable with that situation.
 

What else is next for you and your group?

The next biggest challenge that we’re tackling is PTSD, because of course creating human-encounter scenarios is much more complicated than spiders and dogs. We’re in the midst of developing this so we can basically bring it to people’s homes.

We’ve been working with some military personnel to see if we can basically give a device to a veteran with PTSD, so they can go home and practice on their own.

There’s another possibility for training. Let’s take the example of a police force, which can have a lot of difficulties and mistakes because of lack of exposure and training. They can wear these goggles, get fully geared up, and be placed in encounters with people of different backgrounds, of different severity, with people who could be severely mentally ill or present different challenges for the officers.

Those situations can teach them a lot. I’m the creator of this thing, but even I’m often surprised by how realistic this technology can be. I find myself interacting with avatars the same way I would if they were real humans. I actually had one of my colleagues, when we started launching the programming with the dogs, immediately jump back. It’s just like the animal brain reacts to them.
 

Last question: Do you actually interact with Tony, the tarantula?

Oh, Tony is my friend. Unfortunately, he’s not with our lab at this moment. He’s on a sabbatical at Eastern Michigan University for their clinical trials. But yes, I’ve held him. He’s very friendly.

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

At Wayne State University’s Stress, Trauma, and Anxiety Research Clinic (STARC) in Michigan, researchers are developing novel interventions for treating some very ancient phobias hardwired into the human brain. By using augmented reality as means of conducting exposure therapy, STARC researchers – including Shantanu Madaboosi, Rakesh Ramaswamy, and Lana Grasser – and STARC director Arash Javanbakht, MD, have produced compelling evidence that they can free patients of their often debilitating fears of spiders, dogs, and snakes. Yet their work doesn’t stop there, and research into treating anxiety and posttraumatic stress disorder among first responders and others with high-stress occupations is ongoing.

This news organization spoke with Dr. Javanbakht, a psychiatrist, about the technological advances that have made this work possible; the future of remote-based psychiatry; and his tarantula colleague, Tony.
 

Augmenting exposure therapy

How did you begin using artificial intelligence as a way of delivering exposure therapy?

Exposure therapy is a very effective treatment for phobias, obsessive-compulsive disorder, and PTSD. But the problem we had is that, if someone comes to me and says they’re afraid of dogs, snakes, or spiders, I don’t have those in my office. Or, if its social phobia, I can’t create those scenarios. So, despite being such an effective treatment, it’s not utilized as much as it should be.

Several years ago, I saw a TED talk by the CEO of an augmented reality company who happened to be a neuroscientist. I thought the concept was amazing, because it offered a way to overcome those limitations.

Mixed augmented reality allows us to bring all those feared objects to the clinic. I can bring my Labrador to the office for someone who’s afraid of dogs, and they can get the exposure to that one dog. But we know good exposure therapy needs to be generalizable, with as many different breeds of dogs as possible, and is context dependent. If the patient sees a dog in their neighborhood, their fear response may come back. Doing it in a real-life context, and offering as many contexts as possible, makes it more effective.

Augmented reality allows all of these options because you can have as many different types of virtual objects as you want, and the difference between augmented reality and virtual reality is that augmented reality happens in a real-life context. You wear the goggles and you can walk around the environment and track the object, so the context is more realistic.
 

When did you begin researching augmented reality as a clinical tool?

I became a faculty member here in 2015, right out of my residency training, and I think it was around 2016 or 2017 that we began this work.

I’m very much involved in exposure therapy, utilize it myself, train others, and research how it works and changes the brain. I knew the ins and outs and what would make a better exposure therapy, based on my knowledge of neuroscience.

We spend time thinking about how we can apply these neuroscientific principles in software that can also be easily used by a not very technologically savvy therapist. Because that has been a big barrier when it comes to technology and human use in medicine.

Initially, we had a company create the software for us, but we’ve since brought all the programming inside.

The cool thing about these augmented reality devices is that they have excellent surface mapping. As soon as the person wears the goggles, it automatically maps the surfaces and provides a 3D view of the patient’s environment on the therapist’s computer. Say you’re treating a patient with a fear of spiders. Through drop-down menus, the therapist can choose what type of spider, its color and size, where it should be placed, and the motion. I can choose to move the spider from 6 feet away on the floor to the walls to the ceiling.
 

Virtual phobias, real fear

A big question for a lot of people was if the spiders are virtual, will they be scary, because it has to be realistic enough to create a fear response for the therapy to work. We use a couple of wires that you can put on a person’s finger and hook them up to a tablet or a cell phone. This provides an online measure of a person’s autonomic sympathetic response.

Like a lie detector test?

Exactly. We put that on their fingers and exposed them to a real-life tarantula and to our virtual tarantulas, and the fear response was no different. That means these do create an objective fear reaction in the body.

We also had people who said, “I know this is not real. I won’t be scared.” And when we started the therapy, it was with a tiny spider 5 meters away from them, and they’d lift their legs off the floor.

With the treatment, we’d come to one room and start with a very little spider, far from them. Then gradually we move them up to bigger, more diverse types of spiders, which are moving around. The patient comes near and tries to touch them.

Then at some point, I’d put a spiderweb on the door, put a few spiders on that, open the door, and have the patient walk through it. They kept walking through this spiderweb.

When they were desensitized to these spiders in this context – and as I said, context is important – we’d go to another room. This was darker, more like a basement, and we’d continue the same thing. That would actually take much less time because they already had desensitized a lot.

In our field, sense of control is very important, especially for when a patient goes home. So at the end, I’d leave the room and talk to the patient via a baby monitor. The patient was surrounded by 20 tarantulas, without the prompt moving around the environment.

Now that they’re desensitized to my virtual spiders, the question is, how would that apply to a real spider? So, we had a real live tarantula, whose name was Tony Stark, because we’re the STARC lab. We’d put Tony at the end of a long hallway before the treatment and see how close the patients could get to him.

Everybody who got the treatment was able to touch the tank containing the tarantula. It was only one treatment session; nobody’s was longer than 1 hour, and the average treatment time was 38 minutes.
 

That’s pretty effective.

It’s pretty good, compared with other studies. And I believe this is because of all the components I mentioned: being able to use your real environment; combining it with the real tarantula; the variety of the types of the feared objects; and, of course, giving the patient a sense of autonomy at the end.

Then we had to see how prolonged the effects are. We had them come in 1 week and 1 month after the treatment. I’d remind them of the principles of good exposure therapy and ask them to keep practicing at home between the sessions, looking at pictures and videos. But we never tested who did or did not do it.

After 1 week and 1 month, the effects were either the same or better. A larger number of people at 1 month were able to touch the tarantula than right after treatment.
 

Treating PTSD in first responders

Did you start with spiders and dogs because those are common fears?

We started with spiders because that worked with the initial goal of creating a prototype. Spiders’ behavior is simple enough for the programming, which takes a lot of time. Another reason for choosing spiders was that we had a lot of other studies of real and virtual reality exposure therapy to compare against.

I think another reason for our success is that, when you do real exposure therapy, you have just one scared tarantula in the corner of their tank, and they don’t listen to you. But my spiders listen to me and do exactly what I tell them.

After our initial success, we obtained more funds to expand it to other phobias. The cool thing is that we don’t need separate software for different phobias. You can choose dogs or snakes, add it to the person’s environment, and decide their behaviors.

We just started a clinical trial using dogs, and another group in Turkey is running a clinical trial with dogs. Eastern Michigan University is working with spiders. And a clinic at the University of Nebraska Medical Center is going to start using them in real-world clinics, not for research.

We have another project whose goal is helping reduce the impact of trauma and also treating PTSD in first responders, who are exposed to a lot of horrible things. Rates of PTSD are around 20%-30% among cops, firefighters, and EMS personnel.

They commonly find it very painful being in crowds because the fight-or-flight instinct in the brain is constantly screening for any sign of threat in their environment. We’re working on them walking into an empty room wearing the goggles, and then their therapist can scale the stimulus up and down.

There’ll be two people in front of you talking to each other, and then another group comes in, and people get louder. People can look at you and talk to you. There’s kids running, Fourth of July fireworks, and other things that might bother someone who’s been involved in gun- or explosion-related traumas. You gradually scale up when the person is next to their therapist.

Another thing we’re doing is related to cardiopulmonary resuscitation. If a young person dies in a CPR situation, that is really painful and traumatic. So, for exposure therapy to that, we’re creating a difficult CPR scenario when that person may die. The responder wears the goggles and basically watches a group of people doing CPR while standing next to a therapist who can help them navigate it and then scale it off.

Another goal is combining this with telemedicine, where the person can do it in their real-life environment. Imagine a person with military trauma. You can put them back in the barracks, connected with their psychiatrists via telemedicine. Then we would put humans in military fatigues near them and have them interact with them to feel comfortable with that situation.
 

What else is next for you and your group?

The next biggest challenge that we’re tackling is PTSD, because of course creating human-encounter scenarios is much more complicated than spiders and dogs. We’re in the midst of developing this so we can basically bring it to people’s homes.

We’ve been working with some military personnel to see if we can basically give a device to a veteran with PTSD, so they can go home and practice on their own.

There’s another possibility for training. Let’s take the example of a police force, which can have a lot of difficulties and mistakes because of lack of exposure and training. They can wear these goggles, get fully geared up, and be placed in encounters with people of different backgrounds, of different severity, with people who could be severely mentally ill or present different challenges for the officers.

Those situations can teach them a lot. I’m the creator of this thing, but even I’m often surprised by how realistic this technology can be. I find myself interacting with avatars the same way I would if they were real humans. I actually had one of my colleagues, when we started launching the programming with the dogs, immediately jump back. It’s just like the animal brain reacts to them.
 

Last question: Do you actually interact with Tony, the tarantula?

Oh, Tony is my friend. Unfortunately, he’s not with our lab at this moment. He’s on a sabbatical at Eastern Michigan University for their clinical trials. But yes, I’ve held him. He’s very friendly.

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

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.