Conference Coverage

WASHINGTON ­— Mailing outreach notices for colonoscopies or fecal immunochemical test (FIT) kits may be a great way to increase colorectal cancer (CRC) screening in younger adults, according to a study presented at the annual Digestive Disease Week^® (DDW).

In a comparison of four outreach approaches, sending a FIT kit to people between the ages of 45 and 49 via mail garnered better response rates than opt-in strategies to participate in FIT, inviting them to undergo colonoscopy, or asking them to choose between FIT or colonoscopy. At the same time, when given a choice between colonoscopy and FIT, colonoscopy was preferred across all racial and ethnic groups.

“It is well known that colorectal cancer is the second-leading cause of cancer-related deaths in the United States. The good news is that for the past several decades, we’ve seen a decline in colorectal cancer incidence and mortality in ages 50 and above. However, there has been a recent rise in incidence and mortality in people younger than 50,” said lead author Rebecca Ekeanyanwu, a third-year medical student at Meharry Medical College School of Medicine in Nashville, Tennessee. She was awarded the 2024 AGA Institute Council Healthcare Disparities Research Award for the top oral presentation for research in racial and ethnic health care disparities.

WASHINGTON ­— Mailing outreach notices for colonoscopies or fecal immunochemical test (FIT) kits may be a great way to increase colorectal cancer (CRC) screening in younger adults, according to a study presented at the annual Digestive Disease Week^® (DDW).

In a comparison of four outreach approaches, sending a FIT kit to people between the ages of 45 and 49 via mail garnered better response rates than opt-in strategies to participate in FIT, inviting them to undergo colonoscopy, or asking them to choose between FIT or colonoscopy. At the same time, when given a choice between colonoscopy and FIT, colonoscopy was preferred across all racial and ethnic groups.

“It is well known that colorectal cancer is the second-leading cause of cancer-related deaths in the United States. The good news is that for the past several decades, we’ve seen a decline in colorectal cancer incidence and mortality in ages 50 and above. However, there has been a recent rise in incidence and mortality in people younger than 50,” said lead author Rebecca Ekeanyanwu, a third-year medical student at Meharry Medical College School of Medicine in Nashville, Tennessee. She was awarded the 2024 AGA Institute Council Healthcare Disparities Research Award for the top oral presentation for research in racial and ethnic health care disparities.

WASHINGTON ­— Mailing outreach notices for colonoscopies or fecal immunochemical test (FIT) kits may be a great way to increase colorectal cancer (CRC) screening in younger adults, according to a study presented at the annual Digestive Disease Week^® (DDW).

In a comparison of four outreach approaches, sending a FIT kit to people between the ages of 45 and 49 via mail garnered better response rates than opt-in strategies to participate in FIT, inviting them to undergo colonoscopy, or asking them to choose between FIT or colonoscopy. At the same time, when given a choice between colonoscopy and FIT, colonoscopy was preferred across all racial and ethnic groups.

“It is well known that colorectal cancer is the second-leading cause of cancer-related deaths in the United States. The good news is that for the past several decades, we’ve seen a decline in colorectal cancer incidence and mortality in ages 50 and above. However, there has been a recent rise in incidence and mortality in people younger than 50,” said lead author Rebecca Ekeanyanwu, a third-year medical student at Meharry Medical College School of Medicine in Nashville, Tennessee. She was awarded the 2024 AGA Institute Council Healthcare Disparities Research Award for the top oral presentation for research in racial and ethnic health care disparities.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

Over the past few years, several new, highly effective treatment strategies have improved survival outcomes in patients with early breast cancer.

“We’ve been very fortunate” to see these advances, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, told attendees at the European Society of Medical Oncology (ESMO) Breast Cancer annual congress.

However, Dr. Tolaney noted, these new treatment approaches can come with big limitations — namely, potential overtreatment of some patients as well as short- and long-term toxicities, some of which can be life-threatening.

These caveats have prompted trials exploring strategies to de-escalate therapy, which essentially means providing the right amount of treatment to the right patient at the right time, said Dr. Tolaney. The goal is to “right-size” or “optimize therapy” to maintain strong outcomes while mitigating side effects.

De-escalation studies are “critical to preserving quality of life” and affect the cost-effectiveness of therapy, she explained.

But, she added, de-escalation trials are “not a very attractive strategy to pharmaceutical companies” and can be challenging for researchers to conduct. These trials may, for instance, lack adequate sample sizes and sufficient statistical power, which can interfere with achieving clinically meaningful findings that may affect practice.

That is why carefully designing de-escalation trials is crucial, Dr. Tolaney said.

In her talk at ESMO Breast, Dr. Tolaney highlighted several strategies for designing these trials.

One strategy is to shorten the duration of therapy, said Dr. Tolaney.

This approach was explored in the PHARE and PERSEPHONE trials, which looked at 6 vs 12 months of trastuzumab in nonmetastatic breast cancer. Other trials, such as GeparNuevo and KEYNOTE-522, explored whether adjuvant checkpoint inhibitor therapy was needed, or could be skipped, following neoadjuvant therapy. This approach requires establishing noninferiority, or similar efficacy, between the standard of care and the shorter duration of therapy.

A second strategy is to remove part of the chemotherapy regimen, typically the most toxic agent, Dr. Tolaney continued.

Conducting a prospective, randomized trial exploring this approach in human epidermal growth factor receptor 2–positive (HER2+) early breast cancer, for example, would be difficult for a range of reasons, such as the need to enroll thousands of patients.

Dr. Tolaney and colleagues, however, designed a nonrandomized prospective study — the APT trial — with just over 400 patients to assess adjuvant paclitaxel plus trastuzumab in patients with node-negative HER2+ disease. The open-label, single-arm, phase 2 APT trial found that adjuvant paclitaxel and trastuzumab led to a 10-year recurrence-free interval of 96.3%, 10-year overall survival of 94.3%, and 10-year breast cancer–specific survival of 98.8%.

Outcomes with this adjuvant regimen were comparable to previous findings in historical controls who received doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab or docetaxel, carboplatin, and trastuzumab.

Dr. Tolaney concluded that given few events, “it’s unlikely we need to escalate therapy to do better for most patients,” and the APT regimen “can be considered a reasonable and appealing approach for the majority of patients” with node-negative HER2+ breast cancer.

“A single-arm design for a de-escalation study can be practice-changing but only if there are very few recurrences,” Dr. Tolaney said.

Substituting chemotherapy with a targeted, potentially less-toxic agent is a third de-escalation approach. The ATEMPT trial compared patients receiving trastuzumab emtansine (T-DM1) with those receiving paclitaxel plus trastuzumab followed by maintenance trastuzumab.

Investigators found that de-escalation with T-DM1 was associated with very few recurrences but similar rates of certain adverse events, including grade 2 or higher neurotoxicity, febrile neutropenia, and grade 4 or higher hematologic toxicity.

However, there are questions about how to define “less toxic,” Dr. Tolaney said. The trial found, for instance, that T-DM1 did have some advantages — patients reported better quality of life and experienced less alopecia and neurotoxicity, as well as a less severe impact on fertility.

Understanding the right endpoint to demonstrate less toxicity is critical, “as we start to think about how to replace standard chemotherapies with better targeted drugs,” she added.

The ATEMPT 2.0 trial, which is currently enrolling, will aim to answer some of these questions about defining and demonstrating less toxicity, she said.

Finally, some researchers are attempting to omit chemotherapy altogether with the help of biomarkers. The TAILORx trial, for instance, aimed to stratify patients with early-stage breast cancer by clinical risk factors combined with a 21-gene expression assay and found that adjuvant chemotherapy was not necessary in a large proportion of these women.

On the biomarker front, oncologists might be able to use ctDNA to guide decision-making and personalize therapy, Tolaney said. The presence of ctDNA is associated with an almost 100% likelihood of having a recurrence, whereas its absence suggests better outcomes, she explained.

Oncologists could use the presence or absence of ctDNA to guide next steps — assign patients to follow-up assessments when ctDNA is not present or to standard or experimental treatment when it is present. It may also be possible to leverage the presence of minimal residual disease to help direct treatment choices.

But ctDNA is currently not as perfect a predictor of outcome as it could be, she cautioned. “We need more sensitive assays [so] I’m not sure we’re quite ready to use lack of ctDNA to de-escalate treatment,” she said.

Dr. Tolaney declared relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, and other companies.

A version of this article appeared on Medscape.com .

Over the past few years, several new, highly effective treatment strategies have improved survival outcomes in patients with early breast cancer.

“We’ve been very fortunate” to see these advances, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, told attendees at the European Society of Medical Oncology (ESMO) Breast Cancer annual congress.

However, Dr. Tolaney noted, these new treatment approaches can come with big limitations — namely, potential overtreatment of some patients as well as short- and long-term toxicities, some of which can be life-threatening.

These caveats have prompted trials exploring strategies to de-escalate therapy, which essentially means providing the right amount of treatment to the right patient at the right time, said Dr. Tolaney. The goal is to “right-size” or “optimize therapy” to maintain strong outcomes while mitigating side effects.

De-escalation studies are “critical to preserving quality of life” and affect the cost-effectiveness of therapy, she explained.

But, she added, de-escalation trials are “not a very attractive strategy to pharmaceutical companies” and can be challenging for researchers to conduct. These trials may, for instance, lack adequate sample sizes and sufficient statistical power, which can interfere with achieving clinically meaningful findings that may affect practice.

That is why carefully designing de-escalation trials is crucial, Dr. Tolaney said.

In her talk at ESMO Breast, Dr. Tolaney highlighted several strategies for designing these trials.

One strategy is to shorten the duration of therapy, said Dr. Tolaney.

This approach was explored in the PHARE and PERSEPHONE trials, which looked at 6 vs 12 months of trastuzumab in nonmetastatic breast cancer. Other trials, such as GeparNuevo and KEYNOTE-522, explored whether adjuvant checkpoint inhibitor therapy was needed, or could be skipped, following neoadjuvant therapy. This approach requires establishing noninferiority, or similar efficacy, between the standard of care and the shorter duration of therapy.

A second strategy is to remove part of the chemotherapy regimen, typically the most toxic agent, Dr. Tolaney continued.

Conducting a prospective, randomized trial exploring this approach in human epidermal growth factor receptor 2–positive (HER2+) early breast cancer, for example, would be difficult for a range of reasons, such as the need to enroll thousands of patients.

Dr. Tolaney and colleagues, however, designed a nonrandomized prospective study — the APT trial — with just over 400 patients to assess adjuvant paclitaxel plus trastuzumab in patients with node-negative HER2+ disease. The open-label, single-arm, phase 2 APT trial found that adjuvant paclitaxel and trastuzumab led to a 10-year recurrence-free interval of 96.3%, 10-year overall survival of 94.3%, and 10-year breast cancer–specific survival of 98.8%.

Outcomes with this adjuvant regimen were comparable to previous findings in historical controls who received doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab or docetaxel, carboplatin, and trastuzumab.

Dr. Tolaney concluded that given few events, “it’s unlikely we need to escalate therapy to do better for most patients,” and the APT regimen “can be considered a reasonable and appealing approach for the majority of patients” with node-negative HER2+ breast cancer.

“A single-arm design for a de-escalation study can be practice-changing but only if there are very few recurrences,” Dr. Tolaney said.

Substituting chemotherapy with a targeted, potentially less-toxic agent is a third de-escalation approach. The ATEMPT trial compared patients receiving trastuzumab emtansine (T-DM1) with those receiving paclitaxel plus trastuzumab followed by maintenance trastuzumab.

Investigators found that de-escalation with T-DM1 was associated with very few recurrences but similar rates of certain adverse events, including grade 2 or higher neurotoxicity, febrile neutropenia, and grade 4 or higher hematologic toxicity.

However, there are questions about how to define “less toxic,” Dr. Tolaney said. The trial found, for instance, that T-DM1 did have some advantages — patients reported better quality of life and experienced less alopecia and neurotoxicity, as well as a less severe impact on fertility.

Understanding the right endpoint to demonstrate less toxicity is critical, “as we start to think about how to replace standard chemotherapies with better targeted drugs,” she added.

The ATEMPT 2.0 trial, which is currently enrolling, will aim to answer some of these questions about defining and demonstrating less toxicity, she said.

Finally, some researchers are attempting to omit chemotherapy altogether with the help of biomarkers. The TAILORx trial, for instance, aimed to stratify patients with early-stage breast cancer by clinical risk factors combined with a 21-gene expression assay and found that adjuvant chemotherapy was not necessary in a large proportion of these women.

On the biomarker front, oncologists might be able to use ctDNA to guide decision-making and personalize therapy, Tolaney said. The presence of ctDNA is associated with an almost 100% likelihood of having a recurrence, whereas its absence suggests better outcomes, she explained.

Oncologists could use the presence or absence of ctDNA to guide next steps — assign patients to follow-up assessments when ctDNA is not present or to standard or experimental treatment when it is present. It may also be possible to leverage the presence of minimal residual disease to help direct treatment choices.

But ctDNA is currently not as perfect a predictor of outcome as it could be, she cautioned. “We need more sensitive assays [so] I’m not sure we’re quite ready to use lack of ctDNA to de-escalate treatment,” she said.

Dr. Tolaney declared relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, and other companies.

A version of this article appeared on Medscape.com .

Over the past few years, several new, highly effective treatment strategies have improved survival outcomes in patients with early breast cancer.

“We’ve been very fortunate” to see these advances, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, told attendees at the European Society of Medical Oncology (ESMO) Breast Cancer annual congress.

However, Dr. Tolaney noted, these new treatment approaches can come with big limitations — namely, potential overtreatment of some patients as well as short- and long-term toxicities, some of which can be life-threatening.

These caveats have prompted trials exploring strategies to de-escalate therapy, which essentially means providing the right amount of treatment to the right patient at the right time, said Dr. Tolaney. The goal is to “right-size” or “optimize therapy” to maintain strong outcomes while mitigating side effects.

De-escalation studies are “critical to preserving quality of life” and affect the cost-effectiveness of therapy, she explained.

But, she added, de-escalation trials are “not a very attractive strategy to pharmaceutical companies” and can be challenging for researchers to conduct. These trials may, for instance, lack adequate sample sizes and sufficient statistical power, which can interfere with achieving clinically meaningful findings that may affect practice.

That is why carefully designing de-escalation trials is crucial, Dr. Tolaney said.

In her talk at ESMO Breast, Dr. Tolaney highlighted several strategies for designing these trials.

One strategy is to shorten the duration of therapy, said Dr. Tolaney.

This approach was explored in the PHARE and PERSEPHONE trials, which looked at 6 vs 12 months of trastuzumab in nonmetastatic breast cancer. Other trials, such as GeparNuevo and KEYNOTE-522, explored whether adjuvant checkpoint inhibitor therapy was needed, or could be skipped, following neoadjuvant therapy. This approach requires establishing noninferiority, or similar efficacy, between the standard of care and the shorter duration of therapy.

A second strategy is to remove part of the chemotherapy regimen, typically the most toxic agent, Dr. Tolaney continued.

Conducting a prospective, randomized trial exploring this approach in human epidermal growth factor receptor 2–positive (HER2+) early breast cancer, for example, would be difficult for a range of reasons, such as the need to enroll thousands of patients.

Dr. Tolaney and colleagues, however, designed a nonrandomized prospective study — the APT trial — with just over 400 patients to assess adjuvant paclitaxel plus trastuzumab in patients with node-negative HER2+ disease. The open-label, single-arm, phase 2 APT trial found that adjuvant paclitaxel and trastuzumab led to a 10-year recurrence-free interval of 96.3%, 10-year overall survival of 94.3%, and 10-year breast cancer–specific survival of 98.8%.

Outcomes with this adjuvant regimen were comparable to previous findings in historical controls who received doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab or docetaxel, carboplatin, and trastuzumab.

Dr. Tolaney concluded that given few events, “it’s unlikely we need to escalate therapy to do better for most patients,” and the APT regimen “can be considered a reasonable and appealing approach for the majority of patients” with node-negative HER2+ breast cancer.

“A single-arm design for a de-escalation study can be practice-changing but only if there are very few recurrences,” Dr. Tolaney said.

Substituting chemotherapy with a targeted, potentially less-toxic agent is a third de-escalation approach. The ATEMPT trial compared patients receiving trastuzumab emtansine (T-DM1) with those receiving paclitaxel plus trastuzumab followed by maintenance trastuzumab.

Investigators found that de-escalation with T-DM1 was associated with very few recurrences but similar rates of certain adverse events, including grade 2 or higher neurotoxicity, febrile neutropenia, and grade 4 or higher hematologic toxicity.

However, there are questions about how to define “less toxic,” Dr. Tolaney said. The trial found, for instance, that T-DM1 did have some advantages — patients reported better quality of life and experienced less alopecia and neurotoxicity, as well as a less severe impact on fertility.

Understanding the right endpoint to demonstrate less toxicity is critical, “as we start to think about how to replace standard chemotherapies with better targeted drugs,” she added.

The ATEMPT 2.0 trial, which is currently enrolling, will aim to answer some of these questions about defining and demonstrating less toxicity, she said.

Finally, some researchers are attempting to omit chemotherapy altogether with the help of biomarkers. The TAILORx trial, for instance, aimed to stratify patients with early-stage breast cancer by clinical risk factors combined with a 21-gene expression assay and found that adjuvant chemotherapy was not necessary in a large proportion of these women.

On the biomarker front, oncologists might be able to use ctDNA to guide decision-making and personalize therapy, Tolaney said. The presence of ctDNA is associated with an almost 100% likelihood of having a recurrence, whereas its absence suggests better outcomes, she explained.

Oncologists could use the presence or absence of ctDNA to guide next steps — assign patients to follow-up assessments when ctDNA is not present or to standard or experimental treatment when it is present. It may also be possible to leverage the presence of minimal residual disease to help direct treatment choices.

But ctDNA is currently not as perfect a predictor of outcome as it could be, she cautioned. “We need more sensitive assays [so] I’m not sure we’re quite ready to use lack of ctDNA to de-escalate treatment,” she said.

Dr. Tolaney declared relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, and other companies.

A version of this article appeared on Medscape.com .

Antibody drug conjugates (ADCs) — a class of targeted medications that combine monoclonal antibodies with cytotoxic payloads — are rapidly changing the treatment landscape for patients with metastatic breast cancer.

These medications, which are designed to selectively deliver potent cytotoxic drugs to cancer cells expressing specific surface antigens such as human epidermal growth factor receptor 2 (HER2) and trophoblast cell surface antigen 2 (TROP2), can be highly effective but can also come with significant toxicities.

The latest data on several ADCs — their clinical benefit and safety — were the focus of three presentations here at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

TROPION-Breast01

In her presentation, Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York City, reported additional safety analyses from the phase 3 TROPION-Breast01 trial looking at datopotamab deruxtecan (Dato-DXd) in patients with metastatic hormone receptor–positive (HR+)/HER2− breast cancer resistant to endocrine therapy.

Dato-DXd is an investigational ADC composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

As previously reported by this news organization, median progression-free survival was 6.9 months with Dato-DXd compared with 4.9 months for investigator’s choice of chemotherapy (eribulin mesylate, vinorelbine, gemcitabine, or capecitabine), which translated into a 37% (hazard ratio [HR], 0.63; P < .0001) reduction in risk for disease progression.

In addition, the rate of grade 3 or higher treatment-related adverse events with Dato-DXd was less than half that with standard chemotherapy and led to fewer dose interruptions or reductions, indicating that Dato-DXd is better tolerated.

Dr. Jhaveri focused on three treatment-related adverse events of special interest: Stomatitis/oral mucositis, ocular surface events, and adjudicated drug-related interstitial lung disease.

The rate of any grade oral mucositis with Dato-DXd was 56%, she reported. Most were grade 1 (25%) or grade 2 (23%), with only 7% grade 3. About 13% of patients had a dose reduction for oral mucositis, and only one (0.3%) patient discontinued treatment.

The median time to onset was 22 days, and median time to resolution (for events recovered/resolved at data cutoff) was 36 days.

“The study did provide toxicity management guidelines for patients who experienced stomatitis,” Dr. Jhaveri told attendees. The guidelines highly recommended daily use of a steroid-containing mouthwash as prophylaxis or, if that wasn’t available, an inert, bland mouth rinse.

“Prophylactic cryotherapy — ice chips or ice water held in the mouth throughout the infusion — was also suggested,” she said.

The overall rate of ocular surface events with Dato-DXd was 40%, with most grade 1 (32%) or grade 2 (7%), with only 0.8% grade 3. Rates of dose reduction/interruption (3.3%) and discontinuation (0.3%) were low. Most ocular events were either dry eye (22%) or keratitis (14%).

The incidence of ocular events in the chemotherapy group was 12%, higher than typically seen. The study mandated regular ocular assessments, and Jhaveri noted that it was possible that this contributed to the high rate of low-grade ocular events found in both arms.

Median time to onset of ocular events was 65 days, and median time to resolution was 67 days.

Toxicity management guidelines were also incorporated for ocular events, suggesting daily use of artificial tears and avoidance of contact lenses, Dr. Jhaveri said.

In the Dato-DXd group, there were 12 adjudicated cases (3.3%) of drug-related interstitial lung disease; most were grade 1 (1.4%) and grade 2 (1.1%).

“There was one patient who had a grade 5 event, which was characterized by the investigator as grade 3 pneumonitis, with death attributed to disease progression,” Dr. Jhaveri said. This was subsequently adjudicated to be a grade 5 drug-related death.

The median time to onset of interstitial lung disease was 84.5 days, and median time to resolution was 28 days.

Among other treatment-related adverse events of clinical interest, any grade nausea was the most common event with Dato-DXd, reported by 51% of patients, with only 1.4% grade 3 or higher.

“Prophylactic antiemetic agents are highly recommended prior to infusion of Dato-DXd and on subsequent days as needed,” Dr. Jhaveri said.

Any grade diarrhea was reported in 7.5%, with no grade 3+ diarrhea. Alopecia was reported in 36.4%, of which grade 1 was 21% and grade 2 was 15%.

Summing up, the researcher said the new safety data suggest that Dato-DXd offers “better tolerability” than standard chemotherapy. Coupled with the efficacy data, this further supports “Dato-DXd as a potential new therapeutic option for patients with previously treated, inoperable, or metastatic HR+/HER2− breast cancer.”

DESTINY-Breast02

New data from the phase 3 DESTINY-Breast02 study confirm a long-term survival benefit, as well as a favorable benefit/risk profile of trastuzumab deruxtecan in patients with HER2+ metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1), reported Sung-Bae Kim, MD, PhD, with University of Ulsan College of Medicine, Seoul, Republic of Korea.

In the phase 3 randomized, multicenter, open-label clinical trial, study participants received either trastuzumab deruxtecan or physician’s choice of trastuzumab plus capecitabine or lapatinib or capecitabine. The primary results of the trial were published last year in The Lancet.

As previously reported by this news organization, after median follow-up of 21.5 months in the trastuzumab deruxtecan group and 18.6 months in the treatment of choice group, median progression-free survival was 17.8 months for trastuzumab deruxtecan vs 6.9 months for the physician’s choice group (HR, 0.36; P < .000001).

The latest data show that after a median follow-up of 30.2 months in the trastuzumab deruxtecan group and 20.5 months in the treatment of choice group, median progression-free survival was 16.7 months with trastuzumab deruxtecan vs 5.5 months with the treatment of choice — a 70% reduction in risk for progression (HR, 0.30), Dr. Kim said.

From time of randomization to progression to next line of therapy or death, median progression-free survival was 33.0 months with trastuzumab deruxtecan vs 15.0 with treatment of choice (HR, 0.42).

Median overall survival was 35.7 months with trastuzumab deruxtecan vs 25.0 months with the treatment of choice, with the risk for death reduced by 31% with trastuzumab deruxtecan (HR, 0.69).

The safety profile of trastuzumab deruxtecan continues to be “manageable, with no long-term toxicity observed with longer follow-up,” Dr. Kim told attendees. The most common treatment-emergent adverse events were nausea (73%), fatigue (62%), and vomiting (38%).

There were a total of 46 (11.4%) adjudicated drug-related interstitial lung disease/pneumonitis cases with trastuzumab deruxtecan. Most were grade 1 or 2. This risk did not increase with longer treatment duration; most events occurred within 12 months of starting treatment, Dr. Kim noted.

With longer follow-up, results of DESTINY-Breast02 “reinforce the substantial benefit” of trastuzumab deruxtecan over the treatment of physician’s choice in patients with HER2+ metastatic breast cancer previously treated with T-DM1, he concluded.

Pooled Data from TROPiCS-02 and EVER-132-002

Hope S. Rugo, MD, of the University of California San Francisco, and colleagues reported a meta-analysis of data from the phase 3 TROPiCS-02 and EVER-132-002 trials of the TROP2-directed ADC sacituzumab govitecan vs the treatment of physician’s choice in HR+/HER2− metastatic breast cancer.

In the pooled analysis, median overall survival was significantly longer with sacituzumab govitecan than with the treatment of physician’s choice in the overall population (16.2 vs 12.7 months) and in patients who received prior CDK4/6 inhibitor treatment (15.4 vs 11.5 months). Progression-free survival also favored sacituzumab govitecan.

These results are consistent with trial-level results from TROPICS-02 and EVER-132-002, reinforcing the efficacy benefits of sacituzumab govitecan over the treatment of physician’s choice, the study team said.

Evolving Landscape of ADCs in Breast Cancer

Giuseppe Curigliano, MD, PhD, with the University of Milan, Italy, who served as discussant for the TROPION-Breast01 safety analysis, noted that the clinical landscape of ADCs has “evolved over time.”

He added that despite having a similar target and similar payload, the anti-TROP2 ADCs in development for HR+/HER2− metastatic breast cancer — Dato-DXd, sacituzumab govitecan, and sacituzumab tirumotecan — appear to have different spectrums of toxicity.

Looking ahead, he said it will be important to determine whether toxicity of these agents can be predicted with a pharmacogenomic analysis and whether toxicity is related to the payload or to the linker antibody complex.

“The science and chemistry of ADCs has shown significant promise in terms of clinical activity, but we also need to better understand safety,” Dr. Curigliano told attendees.

“We need to pay attention to signals in the early phase trials of ADCs and be willing to adjust accordingly to maximize therapeutic benefit and minimize toxicity. Team science will be important in the future developmental ADCs,” he added.

TROPION-Breast01 was sponsored by AstraZeneca. DESTINY-Breast-02 was sponsored by Daiichi Sankyo. TROPiCS-02 and EVER-132-002 were supported by Gilead Sciences. Several trial investigators have disclosed various relationships with these and other pharmaceutical companies.

A version of this article appeared on Medscape.com.

Antibody drug conjugates (ADCs) — a class of targeted medications that combine monoclonal antibodies with cytotoxic payloads — are rapidly changing the treatment landscape for patients with metastatic breast cancer.

These medications, which are designed to selectively deliver potent cytotoxic drugs to cancer cells expressing specific surface antigens such as human epidermal growth factor receptor 2 (HER2) and trophoblast cell surface antigen 2 (TROP2), can be highly effective but can also come with significant toxicities.

The latest data on several ADCs — their clinical benefit and safety — were the focus of three presentations here at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

TROPION-Breast01

In her presentation, Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York City, reported additional safety analyses from the phase 3 TROPION-Breast01 trial looking at datopotamab deruxtecan (Dato-DXd) in patients with metastatic hormone receptor–positive (HR+)/HER2− breast cancer resistant to endocrine therapy.

Dato-DXd is an investigational ADC composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

As previously reported by this news organization, median progression-free survival was 6.9 months with Dato-DXd compared with 4.9 months for investigator’s choice of chemotherapy (eribulin mesylate, vinorelbine, gemcitabine, or capecitabine), which translated into a 37% (hazard ratio [HR], 0.63; P < .0001) reduction in risk for disease progression.

In addition, the rate of grade 3 or higher treatment-related adverse events with Dato-DXd was less than half that with standard chemotherapy and led to fewer dose interruptions or reductions, indicating that Dato-DXd is better tolerated.

Dr. Jhaveri focused on three treatment-related adverse events of special interest: Stomatitis/oral mucositis, ocular surface events, and adjudicated drug-related interstitial lung disease.

The rate of any grade oral mucositis with Dato-DXd was 56%, she reported. Most were grade 1 (25%) or grade 2 (23%), with only 7% grade 3. About 13% of patients had a dose reduction for oral mucositis, and only one (0.3%) patient discontinued treatment.

The median time to onset was 22 days, and median time to resolution (for events recovered/resolved at data cutoff) was 36 days.

“The study did provide toxicity management guidelines for patients who experienced stomatitis,” Dr. Jhaveri told attendees. The guidelines highly recommended daily use of a steroid-containing mouthwash as prophylaxis or, if that wasn’t available, an inert, bland mouth rinse.

“Prophylactic cryotherapy — ice chips or ice water held in the mouth throughout the infusion — was also suggested,” she said.

The overall rate of ocular surface events with Dato-DXd was 40%, with most grade 1 (32%) or grade 2 (7%), with only 0.8% grade 3. Rates of dose reduction/interruption (3.3%) and discontinuation (0.3%) were low. Most ocular events were either dry eye (22%) or keratitis (14%).

The incidence of ocular events in the chemotherapy group was 12%, higher than typically seen. The study mandated regular ocular assessments, and Jhaveri noted that it was possible that this contributed to the high rate of low-grade ocular events found in both arms.

Median time to onset of ocular events was 65 days, and median time to resolution was 67 days.

Toxicity management guidelines were also incorporated for ocular events, suggesting daily use of artificial tears and avoidance of contact lenses, Dr. Jhaveri said.

In the Dato-DXd group, there were 12 adjudicated cases (3.3%) of drug-related interstitial lung disease; most were grade 1 (1.4%) and grade 2 (1.1%).

“There was one patient who had a grade 5 event, which was characterized by the investigator as grade 3 pneumonitis, with death attributed to disease progression,” Dr. Jhaveri said. This was subsequently adjudicated to be a grade 5 drug-related death.

The median time to onset of interstitial lung disease was 84.5 days, and median time to resolution was 28 days.

Among other treatment-related adverse events of clinical interest, any grade nausea was the most common event with Dato-DXd, reported by 51% of patients, with only 1.4% grade 3 or higher.

“Prophylactic antiemetic agents are highly recommended prior to infusion of Dato-DXd and on subsequent days as needed,” Dr. Jhaveri said.

Any grade diarrhea was reported in 7.5%, with no grade 3+ diarrhea. Alopecia was reported in 36.4%, of which grade 1 was 21% and grade 2 was 15%.

Summing up, the researcher said the new safety data suggest that Dato-DXd offers “better tolerability” than standard chemotherapy. Coupled with the efficacy data, this further supports “Dato-DXd as a potential new therapeutic option for patients with previously treated, inoperable, or metastatic HR+/HER2− breast cancer.”

DESTINY-Breast02

New data from the phase 3 DESTINY-Breast02 study confirm a long-term survival benefit, as well as a favorable benefit/risk profile of trastuzumab deruxtecan in patients with HER2+ metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1), reported Sung-Bae Kim, MD, PhD, with University of Ulsan College of Medicine, Seoul, Republic of Korea.

In the phase 3 randomized, multicenter, open-label clinical trial, study participants received either trastuzumab deruxtecan or physician’s choice of trastuzumab plus capecitabine or lapatinib or capecitabine. The primary results of the trial were published last year in The Lancet.

As previously reported by this news organization, after median follow-up of 21.5 months in the trastuzumab deruxtecan group and 18.6 months in the treatment of choice group, median progression-free survival was 17.8 months for trastuzumab deruxtecan vs 6.9 months for the physician’s choice group (HR, 0.36; P < .000001).

The latest data show that after a median follow-up of 30.2 months in the trastuzumab deruxtecan group and 20.5 months in the treatment of choice group, median progression-free survival was 16.7 months with trastuzumab deruxtecan vs 5.5 months with the treatment of choice — a 70% reduction in risk for progression (HR, 0.30), Dr. Kim said.

From time of randomization to progression to next line of therapy or death, median progression-free survival was 33.0 months with trastuzumab deruxtecan vs 15.0 with treatment of choice (HR, 0.42).

Median overall survival was 35.7 months with trastuzumab deruxtecan vs 25.0 months with the treatment of choice, with the risk for death reduced by 31% with trastuzumab deruxtecan (HR, 0.69).

The safety profile of trastuzumab deruxtecan continues to be “manageable, with no long-term toxicity observed with longer follow-up,” Dr. Kim told attendees. The most common treatment-emergent adverse events were nausea (73%), fatigue (62%), and vomiting (38%).

There were a total of 46 (11.4%) adjudicated drug-related interstitial lung disease/pneumonitis cases with trastuzumab deruxtecan. Most were grade 1 or 2. This risk did not increase with longer treatment duration; most events occurred within 12 months of starting treatment, Dr. Kim noted.

With longer follow-up, results of DESTINY-Breast02 “reinforce the substantial benefit” of trastuzumab deruxtecan over the treatment of physician’s choice in patients with HER2+ metastatic breast cancer previously treated with T-DM1, he concluded.

Pooled Data from TROPiCS-02 and EVER-132-002

Hope S. Rugo, MD, of the University of California San Francisco, and colleagues reported a meta-analysis of data from the phase 3 TROPiCS-02 and EVER-132-002 trials of the TROP2-directed ADC sacituzumab govitecan vs the treatment of physician’s choice in HR+/HER2− metastatic breast cancer.

In the pooled analysis, median overall survival was significantly longer with sacituzumab govitecan than with the treatment of physician’s choice in the overall population (16.2 vs 12.7 months) and in patients who received prior CDK4/6 inhibitor treatment (15.4 vs 11.5 months). Progression-free survival also favored sacituzumab govitecan.

These results are consistent with trial-level results from TROPICS-02 and EVER-132-002, reinforcing the efficacy benefits of sacituzumab govitecan over the treatment of physician’s choice, the study team said.

Evolving Landscape of ADCs in Breast Cancer

Giuseppe Curigliano, MD, PhD, with the University of Milan, Italy, who served as discussant for the TROPION-Breast01 safety analysis, noted that the clinical landscape of ADCs has “evolved over time.”

He added that despite having a similar target and similar payload, the anti-TROP2 ADCs in development for HR+/HER2− metastatic breast cancer — Dato-DXd, sacituzumab govitecan, and sacituzumab tirumotecan — appear to have different spectrums of toxicity.

Looking ahead, he said it will be important to determine whether toxicity of these agents can be predicted with a pharmacogenomic analysis and whether toxicity is related to the payload or to the linker antibody complex.

“The science and chemistry of ADCs has shown significant promise in terms of clinical activity, but we also need to better understand safety,” Dr. Curigliano told attendees.

“We need to pay attention to signals in the early phase trials of ADCs and be willing to adjust accordingly to maximize therapeutic benefit and minimize toxicity. Team science will be important in the future developmental ADCs,” he added.

TROPION-Breast01 was sponsored by AstraZeneca. DESTINY-Breast-02 was sponsored by Daiichi Sankyo. TROPiCS-02 and EVER-132-002 were supported by Gilead Sciences. Several trial investigators have disclosed various relationships with these and other pharmaceutical companies.

A version of this article appeared on Medscape.com.

Antibody drug conjugates (ADCs) — a class of targeted medications that combine monoclonal antibodies with cytotoxic payloads — are rapidly changing the treatment landscape for patients with metastatic breast cancer.

These medications, which are designed to selectively deliver potent cytotoxic drugs to cancer cells expressing specific surface antigens such as human epidermal growth factor receptor 2 (HER2) and trophoblast cell surface antigen 2 (TROP2), can be highly effective but can also come with significant toxicities.

The latest data on several ADCs — their clinical benefit and safety — were the focus of three presentations here at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

TROPION-Breast01

In her presentation, Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York City, reported additional safety analyses from the phase 3 TROPION-Breast01 trial looking at datopotamab deruxtecan (Dato-DXd) in patients with metastatic hormone receptor–positive (HR+)/HER2− breast cancer resistant to endocrine therapy.

Dato-DXd is an investigational ADC composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

As previously reported by this news organization, median progression-free survival was 6.9 months with Dato-DXd compared with 4.9 months for investigator’s choice of chemotherapy (eribulin mesylate, vinorelbine, gemcitabine, or capecitabine), which translated into a 37% (hazard ratio [HR], 0.63; P < .0001) reduction in risk for disease progression.

In addition, the rate of grade 3 or higher treatment-related adverse events with Dato-DXd was less than half that with standard chemotherapy and led to fewer dose interruptions or reductions, indicating that Dato-DXd is better tolerated.

Dr. Jhaveri focused on three treatment-related adverse events of special interest: Stomatitis/oral mucositis, ocular surface events, and adjudicated drug-related interstitial lung disease.

The rate of any grade oral mucositis with Dato-DXd was 56%, she reported. Most were grade 1 (25%) or grade 2 (23%), with only 7% grade 3. About 13% of patients had a dose reduction for oral mucositis, and only one (0.3%) patient discontinued treatment.

The median time to onset was 22 days, and median time to resolution (for events recovered/resolved at data cutoff) was 36 days.

“The study did provide toxicity management guidelines for patients who experienced stomatitis,” Dr. Jhaveri told attendees. The guidelines highly recommended daily use of a steroid-containing mouthwash as prophylaxis or, if that wasn’t available, an inert, bland mouth rinse.

“Prophylactic cryotherapy — ice chips or ice water held in the mouth throughout the infusion — was also suggested,” she said.

The overall rate of ocular surface events with Dato-DXd was 40%, with most grade 1 (32%) or grade 2 (7%), with only 0.8% grade 3. Rates of dose reduction/interruption (3.3%) and discontinuation (0.3%) were low. Most ocular events were either dry eye (22%) or keratitis (14%).

The incidence of ocular events in the chemotherapy group was 12%, higher than typically seen. The study mandated regular ocular assessments, and Jhaveri noted that it was possible that this contributed to the high rate of low-grade ocular events found in both arms.

Median time to onset of ocular events was 65 days, and median time to resolution was 67 days.

Toxicity management guidelines were also incorporated for ocular events, suggesting daily use of artificial tears and avoidance of contact lenses, Dr. Jhaveri said.

In the Dato-DXd group, there were 12 adjudicated cases (3.3%) of drug-related interstitial lung disease; most were grade 1 (1.4%) and grade 2 (1.1%).

“There was one patient who had a grade 5 event, which was characterized by the investigator as grade 3 pneumonitis, with death attributed to disease progression,” Dr. Jhaveri said. This was subsequently adjudicated to be a grade 5 drug-related death.

The median time to onset of interstitial lung disease was 84.5 days, and median time to resolution was 28 days.

Among other treatment-related adverse events of clinical interest, any grade nausea was the most common event with Dato-DXd, reported by 51% of patients, with only 1.4% grade 3 or higher.

“Prophylactic antiemetic agents are highly recommended prior to infusion of Dato-DXd and on subsequent days as needed,” Dr. Jhaveri said.

Any grade diarrhea was reported in 7.5%, with no grade 3+ diarrhea. Alopecia was reported in 36.4%, of which grade 1 was 21% and grade 2 was 15%.

Summing up, the researcher said the new safety data suggest that Dato-DXd offers “better tolerability” than standard chemotherapy. Coupled with the efficacy data, this further supports “Dato-DXd as a potential new therapeutic option for patients with previously treated, inoperable, or metastatic HR+/HER2− breast cancer.”

DESTINY-Breast02

New data from the phase 3 DESTINY-Breast02 study confirm a long-term survival benefit, as well as a favorable benefit/risk profile of trastuzumab deruxtecan in patients with HER2+ metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1), reported Sung-Bae Kim, MD, PhD, with University of Ulsan College of Medicine, Seoul, Republic of Korea.

In the phase 3 randomized, multicenter, open-label clinical trial, study participants received either trastuzumab deruxtecan or physician’s choice of trastuzumab plus capecitabine or lapatinib or capecitabine. The primary results of the trial were published last year in The Lancet.

As previously reported by this news organization, after median follow-up of 21.5 months in the trastuzumab deruxtecan group and 18.6 months in the treatment of choice group, median progression-free survival was 17.8 months for trastuzumab deruxtecan vs 6.9 months for the physician’s choice group (HR, 0.36; P < .000001).

The latest data show that after a median follow-up of 30.2 months in the trastuzumab deruxtecan group and 20.5 months in the treatment of choice group, median progression-free survival was 16.7 months with trastuzumab deruxtecan vs 5.5 months with the treatment of choice — a 70% reduction in risk for progression (HR, 0.30), Dr. Kim said.

From time of randomization to progression to next line of therapy or death, median progression-free survival was 33.0 months with trastuzumab deruxtecan vs 15.0 with treatment of choice (HR, 0.42).

Median overall survival was 35.7 months with trastuzumab deruxtecan vs 25.0 months with the treatment of choice, with the risk for death reduced by 31% with trastuzumab deruxtecan (HR, 0.69).

The safety profile of trastuzumab deruxtecan continues to be “manageable, with no long-term toxicity observed with longer follow-up,” Dr. Kim told attendees. The most common treatment-emergent adverse events were nausea (73%), fatigue (62%), and vomiting (38%).

There were a total of 46 (11.4%) adjudicated drug-related interstitial lung disease/pneumonitis cases with trastuzumab deruxtecan. Most were grade 1 or 2. This risk did not increase with longer treatment duration; most events occurred within 12 months of starting treatment, Dr. Kim noted.

With longer follow-up, results of DESTINY-Breast02 “reinforce the substantial benefit” of trastuzumab deruxtecan over the treatment of physician’s choice in patients with HER2+ metastatic breast cancer previously treated with T-DM1, he concluded.

Pooled Data from TROPiCS-02 and EVER-132-002

Hope S. Rugo, MD, of the University of California San Francisco, and colleagues reported a meta-analysis of data from the phase 3 TROPiCS-02 and EVER-132-002 trials of the TROP2-directed ADC sacituzumab govitecan vs the treatment of physician’s choice in HR+/HER2− metastatic breast cancer.

In the pooled analysis, median overall survival was significantly longer with sacituzumab govitecan than with the treatment of physician’s choice in the overall population (16.2 vs 12.7 months) and in patients who received prior CDK4/6 inhibitor treatment (15.4 vs 11.5 months). Progression-free survival also favored sacituzumab govitecan.

These results are consistent with trial-level results from TROPICS-02 and EVER-132-002, reinforcing the efficacy benefits of sacituzumab govitecan over the treatment of physician’s choice, the study team said.

Evolving Landscape of ADCs in Breast Cancer

Giuseppe Curigliano, MD, PhD, with the University of Milan, Italy, who served as discussant for the TROPION-Breast01 safety analysis, noted that the clinical landscape of ADCs has “evolved over time.”

He added that despite having a similar target and similar payload, the anti-TROP2 ADCs in development for HR+/HER2− metastatic breast cancer — Dato-DXd, sacituzumab govitecan, and sacituzumab tirumotecan — appear to have different spectrums of toxicity.

Looking ahead, he said it will be important to determine whether toxicity of these agents can be predicted with a pharmacogenomic analysis and whether toxicity is related to the payload or to the linker antibody complex.

“The science and chemistry of ADCs has shown significant promise in terms of clinical activity, but we also need to better understand safety,” Dr. Curigliano told attendees.

“We need to pay attention to signals in the early phase trials of ADCs and be willing to adjust accordingly to maximize therapeutic benefit and minimize toxicity. Team science will be important in the future developmental ADCs,” he added.

TROPION-Breast01 was sponsored by AstraZeneca. DESTINY-Breast-02 was sponsored by Daiichi Sankyo. TROPiCS-02 and EVER-132-002 were supported by Gilead Sciences. Several trial investigators have disclosed various relationships with these and other pharmaceutical companies.

A version of this article appeared on Medscape.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

SAN DIEGO — You can’t treat patients if you can’t find them. But as investigators in a randomized controlled trial showed, a case-finding method based on spirometry results can identify individuals in the community with undiagnosed chronic obstructive pulmonary disease (COPD) or asthma whose lives could be significantly improved with proper care.

Once they have been identified and randomly assigned to be treated by a pulmonologist and asthma-COPD educator according to clinical guidelines, these previously undiagnosed patients have significant improvements in health care utilization, lung function, symptoms, and quality of life compared with patients randomly assigned to treatment by a general practitioner.

“By diagnosing people early and treating them intensively, you can really improve their quality of life,” said lead investigator Shawn D. Aaron, MD, from the Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada.

Even those patients in the study who were randomly assigned to receive care from a general practice physician had improvements in lung function and quality of life, although on a smaller scale than patients assigned to a specialty team, Dr. Aaron said at the American Thoracic Society’s international conference.

He reported results of the study in a late-breaking oral abstract session. The study findings were also published online in The New England Journal of Medicine.
 

Undiagnosed diseases

“The simple problem is that 70% of individuals with asthma or COPD are likely undiagnosed,” Dr. Aaron said.

He noted that the 2007-2012 US National Health and Nutritional Examination Survey found obstructive lung disease in 13% of randomly selected US adults, but 71% of these people had never been diagnosed with asthma or COPD.

“So our questions were in this study: One, can we find adults with undiagnosed asthma or COPD in the community? The second question was: If we find them, are they sick? And the third and most important question was: Can we treat them early and improve their health outcomes?” he said.

Asthma and COPD both present with similar respiratory symptoms, including dyspnea, cough, wheeze, and/or chest tightness, and the two conditions share expiratory airflow obstruction as a common physiologic impairment that can be detected with spirometry.
 

Study details

To identify participants, the investigators hired a commercial survey firm to contact households asking whether any member aged 18 years or older had respiratory symptoms such as shortness of breath, wheezing, increased mucus or sputum production, or prolonged cough in the past 6 months. Those who responded yes were then contacted by a trial coordinator, and the symptomatic household member was asked to complete the Asthma Screening Questionnaire over the phone. Participants aged 60 years or older and those younger than 60 years with a score of 6 or higher on the asthma screen also completed the COPD Diagnostic Questionnaire.

Those with a score of 6 or higher on the asthma screen or 20 or higher on the COPD screen were invited to undergo spirometry at a trial site.

The investigators ultimately identified 508 adults with undiagnosed asthma or COPD and randomly assigned them on an equal basis to an intervention group (253 patients) or control group (255 patients).

In the intervention group treatment was provided by a study pulmonologist and asthma-COPD educator who started guideline-based care. Patients were prescribed inhalers and were taught how to use them, and many were given action plans that included smoking cessation aids, exercise and weight counseling, and vaccinations against influenza and pneumonia.

Participants assigned to the control group would receive usual care provided by their primary care practitioner.
 

Improvements abound

During the 12 months of the study, 92% of patients in the intervention group and 60% in the control group were started on new medications for their condition. 

Only 13.4% of those in the intervention group received either no respiratory treatments or a short-acting beta 2 agonist only during the entire trial period compared with 49.8% of controls, “so the usual care arm was undertreated relative to the intervention arm, and because of that under-treatment we saw a tremendous difference in the primary outcome,” Dr. Aaron said.

The primary outcome, the annualized rate of patient-initiated healthcare utilization for respiratory illness, was significantly lower in the intervention group, translating into an incidence rate ratio of 0.48 (P < .001).

Secondary outcomes were also better in the intervention group. For example, total scores on the St. George Respiratory Questionnaire (SGRQ) declined by 10.2 points from baseline in intervention group compared with a 6.8-point drop in the usual-care group. The mean difference was 3.5 points (P = .009). Lower scores on the 0-100 SGRQ scale indicate better health status.

Similarly, total scores on the COPD Assessment Test, a scale of 0-40 with lower scores indicating better health, declined by 3.8 points and 2.6 points, respectively, over 12 months, for a mean difference of 1.3 points (P = .03).

In addition, those in the intervention arm had a 119-mL improvement in forced expiratory volume in 1 second over the 12 months of the study compared with only a 22-mL improvement in the usual-care group.
 

Translatable results?

Dr. Aaron acknowledged that the investigators could have chosen to keep those who were assigned to the control group unaware of their diagnosis during the study but because all patients enrolled were symptomatic, it would have been unethical to do so. All participants were informed of their diagnosis at randomization, and the information was conveyed to each patient’s primary care practitioner as well.

In fact, many patients in the control group decided to seek treatment for either asthma or COPD after learning of their diagnosis, which may have contributed to improved outcomes in the control arm, he said.

“What this means is if you make the diagnosis early in the community, and at least have them see a primary care practitioner, they will improve their quality of life and their health status,” he concluded.

Ravi Kalhan, MD, MS, from the Northwestern University Feinberg School Of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the case-finding model used in the trial would be difficult to replicate elsewhere.

“This idea of seeking out undiagnosed people by doing spirometry, so-called ‘case finding’ as they described it, testing highly symptomatic people with spirometry, is really challenging in the US, because symptoms are not collected proactively very much,” he said.

Persons with acute respiratory symptoms in the US typically seek healthcare at urgent-care clinics or have unscheduled visits with their primary care physicians, “and by all accounts those people should have spirometry, but they just don’t in the US, as best as I can tell,” he added.

He agreed that getting patients to a specialist can result in better outcomes but said that implementing a systematic approach such as the one described in the study would be extremely difficult in the fragmented US healthcare system.

Dr. Kalhan’s co-moderator, Nuala J. Meyer, MD, MS, from the Hospital of the University of Pennsylvania, Philadelphia, told Chest Physician that “it was interesting that even those who were not in the intervention group but had these details passed on to their primary care physicians still had improvements,” and that it would be beneficial if primary care practitioners were routinely informed about the results of urgent care visits.

She added, however, that in the US the flow of information between urgent care clinics, primary care offices, and specialty clinics is problematic, suggesting that symptomatic patients may not always receive the additional care that they need.

The study was supported by the Canadian Institutes of Health Research. Dr. Aaron, Dr. Kalhan, and Dr. Meyer all reported having no relevant disclosures. 

A version of this article appeared on Medscape.com.

SAN DIEGO — You can’t treat patients if you can’t find them. But as investigators in a randomized controlled trial showed, a case-finding method based on spirometry results can identify individuals in the community with undiagnosed chronic obstructive pulmonary disease (COPD) or asthma whose lives could be significantly improved with proper care.

Once they have been identified and randomly assigned to be treated by a pulmonologist and asthma-COPD educator according to clinical guidelines, these previously undiagnosed patients have significant improvements in health care utilization, lung function, symptoms, and quality of life compared with patients randomly assigned to treatment by a general practitioner.

“By diagnosing people early and treating them intensively, you can really improve their quality of life,” said lead investigator Shawn D. Aaron, MD, from the Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada.

Even those patients in the study who were randomly assigned to receive care from a general practice physician had improvements in lung function and quality of life, although on a smaller scale than patients assigned to a specialty team, Dr. Aaron said at the American Thoracic Society’s international conference.

He reported results of the study in a late-breaking oral abstract session. The study findings were also published online in The New England Journal of Medicine.
 

Undiagnosed diseases

“The simple problem is that 70% of individuals with asthma or COPD are likely undiagnosed,” Dr. Aaron said.

He noted that the 2007-2012 US National Health and Nutritional Examination Survey found obstructive lung disease in 13% of randomly selected US adults, but 71% of these people had never been diagnosed with asthma or COPD.

“So our questions were in this study: One, can we find adults with undiagnosed asthma or COPD in the community? The second question was: If we find them, are they sick? And the third and most important question was: Can we treat them early and improve their health outcomes?” he said.

Asthma and COPD both present with similar respiratory symptoms, including dyspnea, cough, wheeze, and/or chest tightness, and the two conditions share expiratory airflow obstruction as a common physiologic impairment that can be detected with spirometry.
 

Study details

To identify participants, the investigators hired a commercial survey firm to contact households asking whether any member aged 18 years or older had respiratory symptoms such as shortness of breath, wheezing, increased mucus or sputum production, or prolonged cough in the past 6 months. Those who responded yes were then contacted by a trial coordinator, and the symptomatic household member was asked to complete the Asthma Screening Questionnaire over the phone. Participants aged 60 years or older and those younger than 60 years with a score of 6 or higher on the asthma screen also completed the COPD Diagnostic Questionnaire.

Those with a score of 6 or higher on the asthma screen or 20 or higher on the COPD screen were invited to undergo spirometry at a trial site.

The investigators ultimately identified 508 adults with undiagnosed asthma or COPD and randomly assigned them on an equal basis to an intervention group (253 patients) or control group (255 patients).

In the intervention group treatment was provided by a study pulmonologist and asthma-COPD educator who started guideline-based care. Patients were prescribed inhalers and were taught how to use them, and many were given action plans that included smoking cessation aids, exercise and weight counseling, and vaccinations against influenza and pneumonia.

Participants assigned to the control group would receive usual care provided by their primary care practitioner.
 

Improvements abound

During the 12 months of the study, 92% of patients in the intervention group and 60% in the control group were started on new medications for their condition. 

Only 13.4% of those in the intervention group received either no respiratory treatments or a short-acting beta 2 agonist only during the entire trial period compared with 49.8% of controls, “so the usual care arm was undertreated relative to the intervention arm, and because of that under-treatment we saw a tremendous difference in the primary outcome,” Dr. Aaron said.

The primary outcome, the annualized rate of patient-initiated healthcare utilization for respiratory illness, was significantly lower in the intervention group, translating into an incidence rate ratio of 0.48 (P < .001).

Secondary outcomes were also better in the intervention group. For example, total scores on the St. George Respiratory Questionnaire (SGRQ) declined by 10.2 points from baseline in intervention group compared with a 6.8-point drop in the usual-care group. The mean difference was 3.5 points (P = .009). Lower scores on the 0-100 SGRQ scale indicate better health status.

Similarly, total scores on the COPD Assessment Test, a scale of 0-40 with lower scores indicating better health, declined by 3.8 points and 2.6 points, respectively, over 12 months, for a mean difference of 1.3 points (P = .03).

In addition, those in the intervention arm had a 119-mL improvement in forced expiratory volume in 1 second over the 12 months of the study compared with only a 22-mL improvement in the usual-care group.
 

Translatable results?

Dr. Aaron acknowledged that the investigators could have chosen to keep those who were assigned to the control group unaware of their diagnosis during the study but because all patients enrolled were symptomatic, it would have been unethical to do so. All participants were informed of their diagnosis at randomization, and the information was conveyed to each patient’s primary care practitioner as well.

In fact, many patients in the control group decided to seek treatment for either asthma or COPD after learning of their diagnosis, which may have contributed to improved outcomes in the control arm, he said.

“What this means is if you make the diagnosis early in the community, and at least have them see a primary care practitioner, they will improve their quality of life and their health status,” he concluded.

Ravi Kalhan, MD, MS, from the Northwestern University Feinberg School Of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the case-finding model used in the trial would be difficult to replicate elsewhere.

“This idea of seeking out undiagnosed people by doing spirometry, so-called ‘case finding’ as they described it, testing highly symptomatic people with spirometry, is really challenging in the US, because symptoms are not collected proactively very much,” he said.

Persons with acute respiratory symptoms in the US typically seek healthcare at urgent-care clinics or have unscheduled visits with their primary care physicians, “and by all accounts those people should have spirometry, but they just don’t in the US, as best as I can tell,” he added.

He agreed that getting patients to a specialist can result in better outcomes but said that implementing a systematic approach such as the one described in the study would be extremely difficult in the fragmented US healthcare system.

Dr. Kalhan’s co-moderator, Nuala J. Meyer, MD, MS, from the Hospital of the University of Pennsylvania, Philadelphia, told Chest Physician that “it was interesting that even those who were not in the intervention group but had these details passed on to their primary care physicians still had improvements,” and that it would be beneficial if primary care practitioners were routinely informed about the results of urgent care visits.

She added, however, that in the US the flow of information between urgent care clinics, primary care offices, and specialty clinics is problematic, suggesting that symptomatic patients may not always receive the additional care that they need.

The study was supported by the Canadian Institutes of Health Research. Dr. Aaron, Dr. Kalhan, and Dr. Meyer all reported having no relevant disclosures. 

A version of this article appeared on Medscape.com.

SAN DIEGO — You can’t treat patients if you can’t find them. But as investigators in a randomized controlled trial showed, a case-finding method based on spirometry results can identify individuals in the community with undiagnosed chronic obstructive pulmonary disease (COPD) or asthma whose lives could be significantly improved with proper care.

Once they have been identified and randomly assigned to be treated by a pulmonologist and asthma-COPD educator according to clinical guidelines, these previously undiagnosed patients have significant improvements in health care utilization, lung function, symptoms, and quality of life compared with patients randomly assigned to treatment by a general practitioner.

“By diagnosing people early and treating them intensively, you can really improve their quality of life,” said lead investigator Shawn D. Aaron, MD, from the Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada.

Even those patients in the study who were randomly assigned to receive care from a general practice physician had improvements in lung function and quality of life, although on a smaller scale than patients assigned to a specialty team, Dr. Aaron said at the American Thoracic Society’s international conference.

He reported results of the study in a late-breaking oral abstract session. The study findings were also published online in The New England Journal of Medicine.
 

Undiagnosed diseases

“The simple problem is that 70% of individuals with asthma or COPD are likely undiagnosed,” Dr. Aaron said.

He noted that the 2007-2012 US National Health and Nutritional Examination Survey found obstructive lung disease in 13% of randomly selected US adults, but 71% of these people had never been diagnosed with asthma or COPD.

“So our questions were in this study: One, can we find adults with undiagnosed asthma or COPD in the community? The second question was: If we find them, are they sick? And the third and most important question was: Can we treat them early and improve their health outcomes?” he said.

Asthma and COPD both present with similar respiratory symptoms, including dyspnea, cough, wheeze, and/or chest tightness, and the two conditions share expiratory airflow obstruction as a common physiologic impairment that can be detected with spirometry.
 

Study details

To identify participants, the investigators hired a commercial survey firm to contact households asking whether any member aged 18 years or older had respiratory symptoms such as shortness of breath, wheezing, increased mucus or sputum production, or prolonged cough in the past 6 months. Those who responded yes were then contacted by a trial coordinator, and the symptomatic household member was asked to complete the Asthma Screening Questionnaire over the phone. Participants aged 60 years or older and those younger than 60 years with a score of 6 or higher on the asthma screen also completed the COPD Diagnostic Questionnaire.

Those with a score of 6 or higher on the asthma screen or 20 or higher on the COPD screen were invited to undergo spirometry at a trial site.

The investigators ultimately identified 508 adults with undiagnosed asthma or COPD and randomly assigned them on an equal basis to an intervention group (253 patients) or control group (255 patients).

In the intervention group treatment was provided by a study pulmonologist and asthma-COPD educator who started guideline-based care. Patients were prescribed inhalers and were taught how to use them, and many were given action plans that included smoking cessation aids, exercise and weight counseling, and vaccinations against influenza and pneumonia.

Participants assigned to the control group would receive usual care provided by their primary care practitioner.
 

Improvements abound

During the 12 months of the study, 92% of patients in the intervention group and 60% in the control group were started on new medications for their condition. 

Only 13.4% of those in the intervention group received either no respiratory treatments or a short-acting beta 2 agonist only during the entire trial period compared with 49.8% of controls, “so the usual care arm was undertreated relative to the intervention arm, and because of that under-treatment we saw a tremendous difference in the primary outcome,” Dr. Aaron said.

The primary outcome, the annualized rate of patient-initiated healthcare utilization for respiratory illness, was significantly lower in the intervention group, translating into an incidence rate ratio of 0.48 (P < .001).

Secondary outcomes were also better in the intervention group. For example, total scores on the St. George Respiratory Questionnaire (SGRQ) declined by 10.2 points from baseline in intervention group compared with a 6.8-point drop in the usual-care group. The mean difference was 3.5 points (P = .009). Lower scores on the 0-100 SGRQ scale indicate better health status.

Similarly, total scores on the COPD Assessment Test, a scale of 0-40 with lower scores indicating better health, declined by 3.8 points and 2.6 points, respectively, over 12 months, for a mean difference of 1.3 points (P = .03).

In addition, those in the intervention arm had a 119-mL improvement in forced expiratory volume in 1 second over the 12 months of the study compared with only a 22-mL improvement in the usual-care group.
 

Translatable results?

Dr. Aaron acknowledged that the investigators could have chosen to keep those who were assigned to the control group unaware of their diagnosis during the study but because all patients enrolled were symptomatic, it would have been unethical to do so. All participants were informed of their diagnosis at randomization, and the information was conveyed to each patient’s primary care practitioner as well.

In fact, many patients in the control group decided to seek treatment for either asthma or COPD after learning of their diagnosis, which may have contributed to improved outcomes in the control arm, he said.

“What this means is if you make the diagnosis early in the community, and at least have them see a primary care practitioner, they will improve their quality of life and their health status,” he concluded.

Ravi Kalhan, MD, MS, from the Northwestern University Feinberg School Of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the case-finding model used in the trial would be difficult to replicate elsewhere.

“This idea of seeking out undiagnosed people by doing spirometry, so-called ‘case finding’ as they described it, testing highly symptomatic people with spirometry, is really challenging in the US, because symptoms are not collected proactively very much,” he said.

Persons with acute respiratory symptoms in the US typically seek healthcare at urgent-care clinics or have unscheduled visits with their primary care physicians, “and by all accounts those people should have spirometry, but they just don’t in the US, as best as I can tell,” he added.

He agreed that getting patients to a specialist can result in better outcomes but said that implementing a systematic approach such as the one described in the study would be extremely difficult in the fragmented US healthcare system.

Dr. Kalhan’s co-moderator, Nuala J. Meyer, MD, MS, from the Hospital of the University of Pennsylvania, Philadelphia, told Chest Physician that “it was interesting that even those who were not in the intervention group but had these details passed on to their primary care physicians still had improvements,” and that it would be beneficial if primary care practitioners were routinely informed about the results of urgent care visits.

She added, however, that in the US the flow of information between urgent care clinics, primary care offices, and specialty clinics is problematic, suggesting that symptomatic patients may not always receive the additional care that they need.

The study was supported by the Canadian Institutes of Health Research. Dr. Aaron, Dr. Kalhan, and Dr. Meyer all reported having no relevant disclosures. 

A version of this article appeared on Medscape.com.

PHOENIX — Mohs surgery appears to be superior to wide local excision (WLE) in patients with high-stage cutaneous squamous cell carcinoma (cSCC), according to findings from a retrospective study. The benefit was seen across all outcome measures, including rates of recurrence, metastasis, and mortality.

These data support Mohs surgery as being the preferred surgical treatment option for high-stage cSCC, commented lead author David M. Wang, MD, Mohs Micrographic Surgery and Dermatologic Oncology Fellow, at Harvard’s Brigham and Women’s Hospital (BWH)/Dana-Farber Cancer Institute, Boston. “We found that across all outcomes, high-stage cSCC treated with WLE had a roughly twofold greater risk for recurrence, metastasis, or disease-specific death compared to Mohs,” he said at the annual meeting of the American College of Mohs Surgery (ACMS), where he presented the results.

External validation using data from a multicenter cSCC research collaboration from 12 contributing sites from across the United States, as well as international sites, was also conducted. “We performed the external validation by comparing results of the BWH-only cohort, which was the primary study, with the full multicenter data and with the full multicenter data minus the BWH cohort, and the findings were nearly identical in all three analyses,” Dr. Wang said.

Although patients diagnosed with cSCC usually have good outcomes, high-stage disease is associated with a higher risk for recurrence, metastasis, and death. Both Mohs surgery and WLE are used to treat cSCC, but a comparison of outcomes has not been well established in the setting of high-stage cSCC. Comparing the two surgical strategies can be problematic, as both patient and/or tumor characteristics can make it difficult to determine which outcomes can be attributed solely to the treatment type.

Mohs Superior Across the Board

In the retrospective cohort study, Dr. Wang and colleagues aimed to compare the results of Mohs surgery and WLE in patients with high-stage cSCC (BWH Staging System T2b or T3) and used statistical methods to balance baseline patient and tumor characteristics.

“To control for confounding by indication — differences in baseline patient or tumor characteristics — that are associated with both the treatment received and outcomes, we used propensity score weighting so that the baseline characteristics were balanced in the two treatment groups,” Dr. Wang told this news organization. “This statistical method aims to simulate randomization in a randomized controlled trial such that any differences in outcomes after propensity score weighting is attributed solely to the treatment received.”

The study used electronic medical records from a single tertiary care academic institution, and 216 patients with high-stage cSCC who had undergone surgery from January 2000 to December 2019 were included in the analysis. The median follow-up time was 33.1 months.

They found that overall, the risk for all adverse outcomes was lower among patients who had undergone Mohs surgery than among those treated with WLE, with the following results: Rates of local recurrence (5-year CI, 10.8% vs 22.1%, respectively; P = .003), nodal metastasis (11.9% vs 19.3%; P = .04), distant metastasis (4.7% vs 9.0%; P = .09), any recurrence (17.0% vs 34.2%; P < .001), and disease-specific death (8.5% vs 20.3%; P = .001).

“The data supports Mohs surgery as the preferred surgical treatment option for high-stage cSCC in accordance with NCCN [National Comprehensive Cancer Network] guidelines for very high-risk cSCC,” Dr. Wang said. He pointed out that the terminology “very high risk” in NCCN equates to “high stage” in other staging systems (BWH T2b or higher, AJCC T3 or higher).

There is still “a substantial proportion” of patients with high-stage cSCC who are eligible for Mohs but are treated with WLE, he added. “Our hope is that these findings provide additional data to support Mohs as the standard of care for primary surgical treatment of high-stage cSCC.”
 

Supports Benefits of Mohs

Weighing in on the research, Thomas E. Rohrer, MD, a dermatologic surgeon in Chestnut Hill, Massachusetts, noted that this was an excellent study that demonstrates benefits of Mohs surgery over straight excision on essentially all outcomes investigated and measured.

“The data clearly shows that Mohs should be used whenever possible,” he said. “There are some patients and facilities that do not have access or timely access to Mohs, so they would likely proceed with standard wide local excision. Otherwise, if there is the capability to perform Mohs, it would be preferred,” he added.

“There is no benefit to a standard excision over Mohs,” Dr. Rohrer emphasized. “If a surgeon is not sure if they have attained clear margins, they could and often do take a little more tissue to be certain.”

Also asked to comment on the data, Chad L. Prather, MD, a dermatologist in Baton Rouge, Louisiana, said, “We know that Mohs has been used for cancers that are not highly staged and we know it’s better than WLE, but this study shows that it is beneficial for higher stage cancers.”

However, he cautioned that unlike early-stage cancers, where Mohs is usually a definitive treatment, with higher stage disease it is a starting point. “As a takeaway, Mohs is superior, but it needs to be followed through,” he said. “These patients need to be closely followed as they are at a high risk for recurrence and metastasis and may need to be worked up for lymph node involvement and need additional therapy going forward.”

Dr. Prather also pointed out that there are circumstances when WLE may be a more suitable treatment. “Mohs is not very good if there is bony involvement,” he said. “This most often happens when the lesion is on the scalp and has invaded the skull. WLE may still be the preferred choice.”

Additionally, Mohs is not the best choice if the tumor is broken into multiple segments. “In these cases, WLE may be preferred,” Dr. Prather added. “But overall, Mohs is one of the best tools we have, and it stands to reason that it works well for high-risk tumors, as this study shows.”

The study was independently supported. Dr. Wang reported no relevant financial relationships. Dr. Rohrer and Dr. Prather had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — Mohs surgery appears to be superior to wide local excision (WLE) in patients with high-stage cutaneous squamous cell carcinoma (cSCC), according to findings from a retrospective study. The benefit was seen across all outcome measures, including rates of recurrence, metastasis, and mortality.

These data support Mohs surgery as being the preferred surgical treatment option for high-stage cSCC, commented lead author David M. Wang, MD, Mohs Micrographic Surgery and Dermatologic Oncology Fellow, at Harvard’s Brigham and Women’s Hospital (BWH)/Dana-Farber Cancer Institute, Boston. “We found that across all outcomes, high-stage cSCC treated with WLE had a roughly twofold greater risk for recurrence, metastasis, or disease-specific death compared to Mohs,” he said at the annual meeting of the American College of Mohs Surgery (ACMS), where he presented the results.

External validation using data from a multicenter cSCC research collaboration from 12 contributing sites from across the United States, as well as international sites, was also conducted. “We performed the external validation by comparing results of the BWH-only cohort, which was the primary study, with the full multicenter data and with the full multicenter data minus the BWH cohort, and the findings were nearly identical in all three analyses,” Dr. Wang said.

Although patients diagnosed with cSCC usually have good outcomes, high-stage disease is associated with a higher risk for recurrence, metastasis, and death. Both Mohs surgery and WLE are used to treat cSCC, but a comparison of outcomes has not been well established in the setting of high-stage cSCC. Comparing the two surgical strategies can be problematic, as both patient and/or tumor characteristics can make it difficult to determine which outcomes can be attributed solely to the treatment type.

Mohs Superior Across the Board

In the retrospective cohort study, Dr. Wang and colleagues aimed to compare the results of Mohs surgery and WLE in patients with high-stage cSCC (BWH Staging System T2b or T3) and used statistical methods to balance baseline patient and tumor characteristics.

“To control for confounding by indication — differences in baseline patient or tumor characteristics — that are associated with both the treatment received and outcomes, we used propensity score weighting so that the baseline characteristics were balanced in the two treatment groups,” Dr. Wang told this news organization. “This statistical method aims to simulate randomization in a randomized controlled trial such that any differences in outcomes after propensity score weighting is attributed solely to the treatment received.”

The study used electronic medical records from a single tertiary care academic institution, and 216 patients with high-stage cSCC who had undergone surgery from January 2000 to December 2019 were included in the analysis. The median follow-up time was 33.1 months.

They found that overall, the risk for all adverse outcomes was lower among patients who had undergone Mohs surgery than among those treated with WLE, with the following results: Rates of local recurrence (5-year CI, 10.8% vs 22.1%, respectively; P = .003), nodal metastasis (11.9% vs 19.3%; P = .04), distant metastasis (4.7% vs 9.0%; P = .09), any recurrence (17.0% vs 34.2%; P < .001), and disease-specific death (8.5% vs 20.3%; P = .001).

“The data supports Mohs surgery as the preferred surgical treatment option for high-stage cSCC in accordance with NCCN [National Comprehensive Cancer Network] guidelines for very high-risk cSCC,” Dr. Wang said. He pointed out that the terminology “very high risk” in NCCN equates to “high stage” in other staging systems (BWH T2b or higher, AJCC T3 or higher).

There is still “a substantial proportion” of patients with high-stage cSCC who are eligible for Mohs but are treated with WLE, he added. “Our hope is that these findings provide additional data to support Mohs as the standard of care for primary surgical treatment of high-stage cSCC.”
 

Supports Benefits of Mohs

Weighing in on the research, Thomas E. Rohrer, MD, a dermatologic surgeon in Chestnut Hill, Massachusetts, noted that this was an excellent study that demonstrates benefits of Mohs surgery over straight excision on essentially all outcomes investigated and measured.

“The data clearly shows that Mohs should be used whenever possible,” he said. “There are some patients and facilities that do not have access or timely access to Mohs, so they would likely proceed with standard wide local excision. Otherwise, if there is the capability to perform Mohs, it would be preferred,” he added.

“There is no benefit to a standard excision over Mohs,” Dr. Rohrer emphasized. “If a surgeon is not sure if they have attained clear margins, they could and often do take a little more tissue to be certain.”

Also asked to comment on the data, Chad L. Prather, MD, a dermatologist in Baton Rouge, Louisiana, said, “We know that Mohs has been used for cancers that are not highly staged and we know it’s better than WLE, but this study shows that it is beneficial for higher stage cancers.”

However, he cautioned that unlike early-stage cancers, where Mohs is usually a definitive treatment, with higher stage disease it is a starting point. “As a takeaway, Mohs is superior, but it needs to be followed through,” he said. “These patients need to be closely followed as they are at a high risk for recurrence and metastasis and may need to be worked up for lymph node involvement and need additional therapy going forward.”

Dr. Prather also pointed out that there are circumstances when WLE may be a more suitable treatment. “Mohs is not very good if there is bony involvement,” he said. “This most often happens when the lesion is on the scalp and has invaded the skull. WLE may still be the preferred choice.”

Additionally, Mohs is not the best choice if the tumor is broken into multiple segments. “In these cases, WLE may be preferred,” Dr. Prather added. “But overall, Mohs is one of the best tools we have, and it stands to reason that it works well for high-risk tumors, as this study shows.”

The study was independently supported. Dr. Wang reported no relevant financial relationships. Dr. Rohrer and Dr. Prather had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — Mohs surgery appears to be superior to wide local excision (WLE) in patients with high-stage cutaneous squamous cell carcinoma (cSCC), according to findings from a retrospective study. The benefit was seen across all outcome measures, including rates of recurrence, metastasis, and mortality.

These data support Mohs surgery as being the preferred surgical treatment option for high-stage cSCC, commented lead author David M. Wang, MD, Mohs Micrographic Surgery and Dermatologic Oncology Fellow, at Harvard’s Brigham and Women’s Hospital (BWH)/Dana-Farber Cancer Institute, Boston. “We found that across all outcomes, high-stage cSCC treated with WLE had a roughly twofold greater risk for recurrence, metastasis, or disease-specific death compared to Mohs,” he said at the annual meeting of the American College of Mohs Surgery (ACMS), where he presented the results.

External validation using data from a multicenter cSCC research collaboration from 12 contributing sites from across the United States, as well as international sites, was also conducted. “We performed the external validation by comparing results of the BWH-only cohort, which was the primary study, with the full multicenter data and with the full multicenter data minus the BWH cohort, and the findings were nearly identical in all three analyses,” Dr. Wang said.

Although patients diagnosed with cSCC usually have good outcomes, high-stage disease is associated with a higher risk for recurrence, metastasis, and death. Both Mohs surgery and WLE are used to treat cSCC, but a comparison of outcomes has not been well established in the setting of high-stage cSCC. Comparing the two surgical strategies can be problematic, as both patient and/or tumor characteristics can make it difficult to determine which outcomes can be attributed solely to the treatment type.

Mohs Superior Across the Board

In the retrospective cohort study, Dr. Wang and colleagues aimed to compare the results of Mohs surgery and WLE in patients with high-stage cSCC (BWH Staging System T2b or T3) and used statistical methods to balance baseline patient and tumor characteristics.

“To control for confounding by indication — differences in baseline patient or tumor characteristics — that are associated with both the treatment received and outcomes, we used propensity score weighting so that the baseline characteristics were balanced in the two treatment groups,” Dr. Wang told this news organization. “This statistical method aims to simulate randomization in a randomized controlled trial such that any differences in outcomes after propensity score weighting is attributed solely to the treatment received.”

The study used electronic medical records from a single tertiary care academic institution, and 216 patients with high-stage cSCC who had undergone surgery from January 2000 to December 2019 were included in the analysis. The median follow-up time was 33.1 months.

They found that overall, the risk for all adverse outcomes was lower among patients who had undergone Mohs surgery than among those treated with WLE, with the following results: Rates of local recurrence (5-year CI, 10.8% vs 22.1%, respectively; P = .003), nodal metastasis (11.9% vs 19.3%; P = .04), distant metastasis (4.7% vs 9.0%; P = .09), any recurrence (17.0% vs 34.2%; P < .001), and disease-specific death (8.5% vs 20.3%; P = .001).

“The data supports Mohs surgery as the preferred surgical treatment option for high-stage cSCC in accordance with NCCN [National Comprehensive Cancer Network] guidelines for very high-risk cSCC,” Dr. Wang said. He pointed out that the terminology “very high risk” in NCCN equates to “high stage” in other staging systems (BWH T2b or higher, AJCC T3 or higher).

There is still “a substantial proportion” of patients with high-stage cSCC who are eligible for Mohs but are treated with WLE, he added. “Our hope is that these findings provide additional data to support Mohs as the standard of care for primary surgical treatment of high-stage cSCC.”
 

Supports Benefits of Mohs

Weighing in on the research, Thomas E. Rohrer, MD, a dermatologic surgeon in Chestnut Hill, Massachusetts, noted that this was an excellent study that demonstrates benefits of Mohs surgery over straight excision on essentially all outcomes investigated and measured.

“The data clearly shows that Mohs should be used whenever possible,” he said. “There are some patients and facilities that do not have access or timely access to Mohs, so they would likely proceed with standard wide local excision. Otherwise, if there is the capability to perform Mohs, it would be preferred,” he added.

“There is no benefit to a standard excision over Mohs,” Dr. Rohrer emphasized. “If a surgeon is not sure if they have attained clear margins, they could and often do take a little more tissue to be certain.”

Also asked to comment on the data, Chad L. Prather, MD, a dermatologist in Baton Rouge, Louisiana, said, “We know that Mohs has been used for cancers that are not highly staged and we know it’s better than WLE, but this study shows that it is beneficial for higher stage cancers.”

However, he cautioned that unlike early-stage cancers, where Mohs is usually a definitive treatment, with higher stage disease it is a starting point. “As a takeaway, Mohs is superior, but it needs to be followed through,” he said. “These patients need to be closely followed as they are at a high risk for recurrence and metastasis and may need to be worked up for lymph node involvement and need additional therapy going forward.”

Dr. Prather also pointed out that there are circumstances when WLE may be a more suitable treatment. “Mohs is not very good if there is bony involvement,” he said. “This most often happens when the lesion is on the scalp and has invaded the skull. WLE may still be the preferred choice.”

Additionally, Mohs is not the best choice if the tumor is broken into multiple segments. “In these cases, WLE may be preferred,” Dr. Prather added. “But overall, Mohs is one of the best tools we have, and it stands to reason that it works well for high-risk tumors, as this study shows.”

The study was independently supported. Dr. Wang reported no relevant financial relationships. Dr. Rohrer and Dr. Prather had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — A lifestyle intervention focused on diet and exercise can improve cardiac function and the quality of life for patients with pulmonary arterial hypertension (PAH), results of a randomized clinical trial show.

At 12 weeks of follow-up, patients with PAH who were randomized to undergo a diet and cardiovascular exercise program had improved right ventricular function, better exercise capacity, and improved quality of life compared with patients randomized to the standard of care.

In addition, for those participants in the diet and exercise group who lost weight, right ventricular glucose uptake improved, reported Gustavo A. Heresi, MD, MS of the division of pulmonary medicine at the Cleveland Clinic.

Neil Osterweil/MDedge News

The intervention did not, however, have an effect on insulin sensitivity, suggesting that insulin resistance is not a significant pathological mechanism in PAH, he said in an oral abstract session at the American Thoracic Society’s international conference.

“With these data, in the context of prior studies showing the benefits of exercise interventions, we believe that diet and exercise should be incorporated and thought of as part of the treatment armamentarium for pulmonary arterial hypertension,” he said.

Despite the availability of 14 FDA-approved medications for PAH, the disease is incurable. It is marked by progressive pulmonary vasoconstriction, pulmonary vascular remodeling, fibrosis and inflammation, in situ thrombosis, and right ventricular failure.

Because abnormalities in both glucose and insulin metabolism are prevalent and associated with decreased survival in patients with PAH, Dr. Heresi and colleagues designed a randomized trial to test the hypothesis that a diet and exercise intervention could improve insulin sensitivity and right ventricular function.
 

PHINE details

In the study, dubbed Pulmonary Arterial Hypertension Improvement with Nutrition and Exercise (PHINE), the investigators enrolled adults with group 1 PAH who were stable on PAH medications for at least 2 months. Patients with portopulmonary hypertension, New York Heart Association (NYHA) class IV heart failure, syncope, or on supplemental oxygen greater than 4 liters per minute were excluded.

The patients were screened with a graded exercise test, intravenous glucose tolerance test, and other measures at baseline, and after stratification by NYHA class and tricuspid annular plane systolic excursion (TAPSE) score were randomized to the intervention arm (16 patients) or standard of care control arm (14 patients).

The intervention consisted of supervised exercise training for 50-60 minutes on a treadmill at 80%-85% of the patient’s maximum heart rate 5 days per week, plus weekly counseling on a combination low glycemic index/Mediterranean dietary pattern. The diet portion included olive oil as the primary fat source, three 1-ounce servings of nuts and peanuts weekly, fish and legumes at a minimum of 3 servings weekly, and no sugar-sweetened beverage, commercial bakery products, pastries, white breads, white rice, or white potatoes.
 

Results

At the conclusion of the study at 12 weeks there were no statistically significant differences between the groups in either insulin sensitivity or right ventricular strain.

However, patients in the intervention arm had significant improvements compared with controls in mean RV function as measured by TAPSE, improved exercise capacity as measured by peak oxygen uptake and 6-minute walking distance, quality of life as measured by EmPHasis-10 health-related quality of life score, and NYHA functional class.

As noted, right ventricular glucose uptake was improved among those patients in the intervention group who lost weight over the study period.
 

Worth trying

Ravi Kalhan, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the study results show promise.

“We’re so centered on what’s the next big pharmacotherapy you can give to fix the disease, but sometimes maybe we should be pushing lifestyle interventions that are impactful, and they have biologic mechanisms — it’s not just that you got in better shape, but right ventricular function also improves. I’m pretty drawn to that sort of thing,” he said.

“That’s a pretty major effect over a 3-month intervention,” agreed co-moderator Nuala J. Meyer, MD, MS, ATSF, of the Hospital of the University of Pennsylvania.

The PHINE trial was supported by National Institute of Health grants. Dr. Heresi, Dr. Kalhan, and Dr. Meyer reported no conflicts of interest.

SAN DIEGO — A lifestyle intervention focused on diet and exercise can improve cardiac function and the quality of life for patients with pulmonary arterial hypertension (PAH), results of a randomized clinical trial show.

At 12 weeks of follow-up, patients with PAH who were randomized to undergo a diet and cardiovascular exercise program had improved right ventricular function, better exercise capacity, and improved quality of life compared with patients randomized to the standard of care.

In addition, for those participants in the diet and exercise group who lost weight, right ventricular glucose uptake improved, reported Gustavo A. Heresi, MD, MS of the division of pulmonary medicine at the Cleveland Clinic.

Neil Osterweil/MDedge News

The intervention did not, however, have an effect on insulin sensitivity, suggesting that insulin resistance is not a significant pathological mechanism in PAH, he said in an oral abstract session at the American Thoracic Society’s international conference.

“With these data, in the context of prior studies showing the benefits of exercise interventions, we believe that diet and exercise should be incorporated and thought of as part of the treatment armamentarium for pulmonary arterial hypertension,” he said.

Despite the availability of 14 FDA-approved medications for PAH, the disease is incurable. It is marked by progressive pulmonary vasoconstriction, pulmonary vascular remodeling, fibrosis and inflammation, in situ thrombosis, and right ventricular failure.

Because abnormalities in both glucose and insulin metabolism are prevalent and associated with decreased survival in patients with PAH, Dr. Heresi and colleagues designed a randomized trial to test the hypothesis that a diet and exercise intervention could improve insulin sensitivity and right ventricular function.
 

PHINE details

In the study, dubbed Pulmonary Arterial Hypertension Improvement with Nutrition and Exercise (PHINE), the investigators enrolled adults with group 1 PAH who were stable on PAH medications for at least 2 months. Patients with portopulmonary hypertension, New York Heart Association (NYHA) class IV heart failure, syncope, or on supplemental oxygen greater than 4 liters per minute were excluded.

The patients were screened with a graded exercise test, intravenous glucose tolerance test, and other measures at baseline, and after stratification by NYHA class and tricuspid annular plane systolic excursion (TAPSE) score were randomized to the intervention arm (16 patients) or standard of care control arm (14 patients).

The intervention consisted of supervised exercise training for 50-60 minutes on a treadmill at 80%-85% of the patient’s maximum heart rate 5 days per week, plus weekly counseling on a combination low glycemic index/Mediterranean dietary pattern. The diet portion included olive oil as the primary fat source, three 1-ounce servings of nuts and peanuts weekly, fish and legumes at a minimum of 3 servings weekly, and no sugar-sweetened beverage, commercial bakery products, pastries, white breads, white rice, or white potatoes.
 

Results

At the conclusion of the study at 12 weeks there were no statistically significant differences between the groups in either insulin sensitivity or right ventricular strain.

However, patients in the intervention arm had significant improvements compared with controls in mean RV function as measured by TAPSE, improved exercise capacity as measured by peak oxygen uptake and 6-minute walking distance, quality of life as measured by EmPHasis-10 health-related quality of life score, and NYHA functional class.

As noted, right ventricular glucose uptake was improved among those patients in the intervention group who lost weight over the study period.
 

Worth trying

Ravi Kalhan, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the study results show promise.

“We’re so centered on what’s the next big pharmacotherapy you can give to fix the disease, but sometimes maybe we should be pushing lifestyle interventions that are impactful, and they have biologic mechanisms — it’s not just that you got in better shape, but right ventricular function also improves. I’m pretty drawn to that sort of thing,” he said.

“That’s a pretty major effect over a 3-month intervention,” agreed co-moderator Nuala J. Meyer, MD, MS, ATSF, of the Hospital of the University of Pennsylvania.

The PHINE trial was supported by National Institute of Health grants. Dr. Heresi, Dr. Kalhan, and Dr. Meyer reported no conflicts of interest.

SAN DIEGO — A lifestyle intervention focused on diet and exercise can improve cardiac function and the quality of life for patients with pulmonary arterial hypertension (PAH), results of a randomized clinical trial show.

At 12 weeks of follow-up, patients with PAH who were randomized to undergo a diet and cardiovascular exercise program had improved right ventricular function, better exercise capacity, and improved quality of life compared with patients randomized to the standard of care.

In addition, for those participants in the diet and exercise group who lost weight, right ventricular glucose uptake improved, reported Gustavo A. Heresi, MD, MS of the division of pulmonary medicine at the Cleveland Clinic.

Neil Osterweil/MDedge News

The intervention did not, however, have an effect on insulin sensitivity, suggesting that insulin resistance is not a significant pathological mechanism in PAH, he said in an oral abstract session at the American Thoracic Society’s international conference.

“With these data, in the context of prior studies showing the benefits of exercise interventions, we believe that diet and exercise should be incorporated and thought of as part of the treatment armamentarium for pulmonary arterial hypertension,” he said.

Despite the availability of 14 FDA-approved medications for PAH, the disease is incurable. It is marked by progressive pulmonary vasoconstriction, pulmonary vascular remodeling, fibrosis and inflammation, in situ thrombosis, and right ventricular failure.

Because abnormalities in both glucose and insulin metabolism are prevalent and associated with decreased survival in patients with PAH, Dr. Heresi and colleagues designed a randomized trial to test the hypothesis that a diet and exercise intervention could improve insulin sensitivity and right ventricular function.
 

PHINE details

In the study, dubbed Pulmonary Arterial Hypertension Improvement with Nutrition and Exercise (PHINE), the investigators enrolled adults with group 1 PAH who were stable on PAH medications for at least 2 months. Patients with portopulmonary hypertension, New York Heart Association (NYHA) class IV heart failure, syncope, or on supplemental oxygen greater than 4 liters per minute were excluded.

The patients were screened with a graded exercise test, intravenous glucose tolerance test, and other measures at baseline, and after stratification by NYHA class and tricuspid annular plane systolic excursion (TAPSE) score were randomized to the intervention arm (16 patients) or standard of care control arm (14 patients).

The intervention consisted of supervised exercise training for 50-60 minutes on a treadmill at 80%-85% of the patient’s maximum heart rate 5 days per week, plus weekly counseling on a combination low glycemic index/Mediterranean dietary pattern. The diet portion included olive oil as the primary fat source, three 1-ounce servings of nuts and peanuts weekly, fish and legumes at a minimum of 3 servings weekly, and no sugar-sweetened beverage, commercial bakery products, pastries, white breads, white rice, or white potatoes.
 

Results

At the conclusion of the study at 12 weeks there were no statistically significant differences between the groups in either insulin sensitivity or right ventricular strain.

However, patients in the intervention arm had significant improvements compared with controls in mean RV function as measured by TAPSE, improved exercise capacity as measured by peak oxygen uptake and 6-minute walking distance, quality of life as measured by EmPHasis-10 health-related quality of life score, and NYHA functional class.

As noted, right ventricular glucose uptake was improved among those patients in the intervention group who lost weight over the study period.
 

Worth trying

Ravi Kalhan, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the study results show promise.

“We’re so centered on what’s the next big pharmacotherapy you can give to fix the disease, but sometimes maybe we should be pushing lifestyle interventions that are impactful, and they have biologic mechanisms — it’s not just that you got in better shape, but right ventricular function also improves. I’m pretty drawn to that sort of thing,” he said.

“That’s a pretty major effect over a 3-month intervention,” agreed co-moderator Nuala J. Meyer, MD, MS, ATSF, of the Hospital of the University of Pennsylvania.

The PHINE trial was supported by National Institute of Health grants. Dr. Heresi, Dr. Kalhan, and Dr. Meyer reported no conflicts of interest.