Conference Coverage

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

SAN FRANCISCO – No one yet has figured out how to shrink doctors so they can make house calls inside the human blood stream as they did in the science fiction movie “Fantastic Voyage.” But the founders of a gastroenterology startup think they have the next best thing – a remote-controlled robot so small it can be swallowed like a pill.

The concept captured the imagination of a panel of judges earlier this month at the 2023 American Gastroenterological Association Tech Summit where it was named the winner of the annual Shark Tank innovation competition. The AGA Tech Summit and Shark Tank are the flagship events of the AGA Center for GI Innovation and Technology.

“This could be a game-changing investment down the line,” one of the judges, Amrita Sethi, MD, from Columbia University Medical Center in New York, said in an interview.

Vidyard Video

COURTESY AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Hawyard, Calif.–based Endiatx is early in its voyage. The disposable motorized pill, called PillBot, swims through the stomach beaming video back to its operators, but CEO Torrey Smith, an aerospace engineer, sees future generations of the device operating on any diseased tissues that can be treated with surgery. “We believe teeny robots can go anywhere in the body,” he said.

The company executives envision that one day, robots small enough to enter the human brain will be able to eat away at tumors. “Imagine having your brain surgery while you’re on a ride at Disneyland,” said Endiatx cofounder and chair Alex Luebke. If that sounds fanciful, Mr. Smith cites a case report of a botfly larva that wormed its way into a human skull and ate a golf-ball sized chunk of brain.

Endiatx has raised $3 million and sent 24 of its robots swimming into the stomachs of its founding team. Mr. Smith himself has swallowed 15. Operators can use an external device with a joystick. Engineers have experimented with an Xbox video game controller to navigate around the stomach. The procedure requires no anesthesia.

The company expects to apply for Food and Drug Administration approval in 2025 or 2026. Mr. Smith is hoping the agency will approve it quickly because the robot pills are similar enough to passive camera pills that have been on the market for years.

But he also sees it as a crucial step forward because controlling the robot with three electric motors squirting water in six directions will allow physicians to point it at what they really need to see, not just hope to get a lucky shot of a problem area as the device floats by.

The most immediate technical challenge is improving the quality of the pill’s video. “We’re evaluating different cameras but we know we can’t be inferior on the imaging side,” Mr. Smith said.

Attention from the AGA is crucial because the team of engineers wants physicians to help it improve the robot pill, Mr. Luebeke said. “We can build anything, but we need guidance about what the market needs. Doctors have to say, ‘We need you to tweak it this way or that way.’ ”

The business opportunity is large, Mr. Smith said, with 7.5 million upper endoscopies out of 223 million endoscopic procedures done per year in the United States.

Endiatx figures the gross margin on procedures with the robot pills is 90%-95% because the manufacturing cost is about $50 per pill, but physicians can bill $500 for them using existing CPT codes for passive pill cameras.

Dr. Sethi said the robot pill stood out among other contenders because of the dire need for improved endoscopy technology.

Endiatx will represent AGA at the 2023 Digestive Disease Week® (DDW) Shark Tank pitch competition.

Four other finalists

The choice that received the most votes from the audience was Ezalife’s Button Huggie, a device for securing gastrostomy and cecostomy buttons. It includes a reusable, child-proof lid with a disposable, biodegradable, gauze sponge and a base layer held in place with a long-wearing adhesive. This prevents button movement in the tract, which can delay wound healing and lead to complications. In addition, the Button Huggie is much easier to put in place. “Our device is novel, with no direct competitors,” said CTO/COO Tyler Mironuck.

Currently patients are advised to fasten gastrostomy and cecostomy buttons with tape, but the buttons are dislodged 7% of the time, he said. The company estimates that patients spend an average of $100 a month on tape and gauze. The Button Huggie can be manufactured for $56, and the company envisions selling them for $300.

The device is exempt from needing a 510K FDA approval, so it can get to the market quickly. Nevertheless, the company is conducting a clinical trial with 200 patients at five children’s hospitals, Mr. Mironuck said.

NovaScan was a finalist for nsCanary, a device that uses electrical impedance to detect cancer. The device hinges on the company’s discovery that the Cole relaxation frequency is orders of magnitude different for cancerous and benign tissue, yet not affected by mass. By measuring this frequency, the nsCanary can find cancer in tissue acquired through biopsy forceps, snare polypectomy, mucosal resection, and endoscopic ultrasound-guided fine needle biopsy. It works in seconds without the need to interpret images.

Atlas Endoscopy was recognized for REN, a robotic colonoscopy system. The operator uses an external actuating magnet above the patient to guide a disposable ultracompliant endoscope through the colon. The company says this form of navigation prevents looping, reduces pain, and minimizes tissue stress.

Limaca Medical was recognized for Precision, a motorized, automated, rotational cutting and coring needle for endoscopic ultrasound biopsy. Manual biopsy needles now on the market require repeat passes in and out of the endoscope to obtain fragments of tissue, but Precision obtains larger intact samples of tumor tissue in a single pass.

Dr. Sethi has served as a consultant for Boston Scientific, Medtronic and Olympus; as a board member for EndoSound and has received grant support from FUJIFILM.
 

SAN FRANCISCO – No one yet has figured out how to shrink doctors so they can make house calls inside the human blood stream as they did in the science fiction movie “Fantastic Voyage.” But the founders of a gastroenterology startup think they have the next best thing – a remote-controlled robot so small it can be swallowed like a pill.

The concept captured the imagination of a panel of judges earlier this month at the 2023 American Gastroenterological Association Tech Summit where it was named the winner of the annual Shark Tank innovation competition. The AGA Tech Summit and Shark Tank are the flagship events of the AGA Center for GI Innovation and Technology.

“This could be a game-changing investment down the line,” one of the judges, Amrita Sethi, MD, from Columbia University Medical Center in New York, said in an interview.

Vidyard Video

COURTESY AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Hawyard, Calif.–based Endiatx is early in its voyage. The disposable motorized pill, called PillBot, swims through the stomach beaming video back to its operators, but CEO Torrey Smith, an aerospace engineer, sees future generations of the device operating on any diseased tissues that can be treated with surgery. “We believe teeny robots can go anywhere in the body,” he said.

The company executives envision that one day, robots small enough to enter the human brain will be able to eat away at tumors. “Imagine having your brain surgery while you’re on a ride at Disneyland,” said Endiatx cofounder and chair Alex Luebke. If that sounds fanciful, Mr. Smith cites a case report of a botfly larva that wormed its way into a human skull and ate a golf-ball sized chunk of brain.

Endiatx has raised $3 million and sent 24 of its robots swimming into the stomachs of its founding team. Mr. Smith himself has swallowed 15. Operators can use an external device with a joystick. Engineers have experimented with an Xbox video game controller to navigate around the stomach. The procedure requires no anesthesia.

The company expects to apply for Food and Drug Administration approval in 2025 or 2026. Mr. Smith is hoping the agency will approve it quickly because the robot pills are similar enough to passive camera pills that have been on the market for years.

But he also sees it as a crucial step forward because controlling the robot with three electric motors squirting water in six directions will allow physicians to point it at what they really need to see, not just hope to get a lucky shot of a problem area as the device floats by.

The most immediate technical challenge is improving the quality of the pill’s video. “We’re evaluating different cameras but we know we can’t be inferior on the imaging side,” Mr. Smith said.

Attention from the AGA is crucial because the team of engineers wants physicians to help it improve the robot pill, Mr. Luebeke said. “We can build anything, but we need guidance about what the market needs. Doctors have to say, ‘We need you to tweak it this way or that way.’ ”

The business opportunity is large, Mr. Smith said, with 7.5 million upper endoscopies out of 223 million endoscopic procedures done per year in the United States.

Endiatx figures the gross margin on procedures with the robot pills is 90%-95% because the manufacturing cost is about $50 per pill, but physicians can bill $500 for them using existing CPT codes for passive pill cameras.

Dr. Sethi said the robot pill stood out among other contenders because of the dire need for improved endoscopy technology.

Endiatx will represent AGA at the 2023 Digestive Disease Week® (DDW) Shark Tank pitch competition.

Four other finalists

The choice that received the most votes from the audience was Ezalife’s Button Huggie, a device for securing gastrostomy and cecostomy buttons. It includes a reusable, child-proof lid with a disposable, biodegradable, gauze sponge and a base layer held in place with a long-wearing adhesive. This prevents button movement in the tract, which can delay wound healing and lead to complications. In addition, the Button Huggie is much easier to put in place. “Our device is novel, with no direct competitors,” said CTO/COO Tyler Mironuck.

Currently patients are advised to fasten gastrostomy and cecostomy buttons with tape, but the buttons are dislodged 7% of the time, he said. The company estimates that patients spend an average of $100 a month on tape and gauze. The Button Huggie can be manufactured for $56, and the company envisions selling them for $300.

The device is exempt from needing a 510K FDA approval, so it can get to the market quickly. Nevertheless, the company is conducting a clinical trial with 200 patients at five children’s hospitals, Mr. Mironuck said.

NovaScan was a finalist for nsCanary, a device that uses electrical impedance to detect cancer. The device hinges on the company’s discovery that the Cole relaxation frequency is orders of magnitude different for cancerous and benign tissue, yet not affected by mass. By measuring this frequency, the nsCanary can find cancer in tissue acquired through biopsy forceps, snare polypectomy, mucosal resection, and endoscopic ultrasound-guided fine needle biopsy. It works in seconds without the need to interpret images.

Atlas Endoscopy was recognized for REN, a robotic colonoscopy system. The operator uses an external actuating magnet above the patient to guide a disposable ultracompliant endoscope through the colon. The company says this form of navigation prevents looping, reduces pain, and minimizes tissue stress.

Limaca Medical was recognized for Precision, a motorized, automated, rotational cutting and coring needle for endoscopic ultrasound biopsy. Manual biopsy needles now on the market require repeat passes in and out of the endoscope to obtain fragments of tissue, but Precision obtains larger intact samples of tumor tissue in a single pass.

Dr. Sethi has served as a consultant for Boston Scientific, Medtronic and Olympus; as a board member for EndoSound and has received grant support from FUJIFILM.
 

SAN FRANCISCO – No one yet has figured out how to shrink doctors so they can make house calls inside the human blood stream as they did in the science fiction movie “Fantastic Voyage.” But the founders of a gastroenterology startup think they have the next best thing – a remote-controlled robot so small it can be swallowed like a pill.

The concept captured the imagination of a panel of judges earlier this month at the 2023 American Gastroenterological Association Tech Summit where it was named the winner of the annual Shark Tank innovation competition. The AGA Tech Summit and Shark Tank are the flagship events of the AGA Center for GI Innovation and Technology.

“This could be a game-changing investment down the line,” one of the judges, Amrita Sethi, MD, from Columbia University Medical Center in New York, said in an interview.

Vidyard Video

COURTESY AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Hawyard, Calif.–based Endiatx is early in its voyage. The disposable motorized pill, called PillBot, swims through the stomach beaming video back to its operators, but CEO Torrey Smith, an aerospace engineer, sees future generations of the device operating on any diseased tissues that can be treated with surgery. “We believe teeny robots can go anywhere in the body,” he said.

The company executives envision that one day, robots small enough to enter the human brain will be able to eat away at tumors. “Imagine having your brain surgery while you’re on a ride at Disneyland,” said Endiatx cofounder and chair Alex Luebke. If that sounds fanciful, Mr. Smith cites a case report of a botfly larva that wormed its way into a human skull and ate a golf-ball sized chunk of brain.

Endiatx has raised $3 million and sent 24 of its robots swimming into the stomachs of its founding team. Mr. Smith himself has swallowed 15. Operators can use an external device with a joystick. Engineers have experimented with an Xbox video game controller to navigate around the stomach. The procedure requires no anesthesia.

The company expects to apply for Food and Drug Administration approval in 2025 or 2026. Mr. Smith is hoping the agency will approve it quickly because the robot pills are similar enough to passive camera pills that have been on the market for years.

But he also sees it as a crucial step forward because controlling the robot with three electric motors squirting water in six directions will allow physicians to point it at what they really need to see, not just hope to get a lucky shot of a problem area as the device floats by.

The most immediate technical challenge is improving the quality of the pill’s video. “We’re evaluating different cameras but we know we can’t be inferior on the imaging side,” Mr. Smith said.

Attention from the AGA is crucial because the team of engineers wants physicians to help it improve the robot pill, Mr. Luebeke said. “We can build anything, but we need guidance about what the market needs. Doctors have to say, ‘We need you to tweak it this way or that way.’ ”

The business opportunity is large, Mr. Smith said, with 7.5 million upper endoscopies out of 223 million endoscopic procedures done per year in the United States.

Endiatx figures the gross margin on procedures with the robot pills is 90%-95% because the manufacturing cost is about $50 per pill, but physicians can bill $500 for them using existing CPT codes for passive pill cameras.

Dr. Sethi said the robot pill stood out among other contenders because of the dire need for improved endoscopy technology.

Endiatx will represent AGA at the 2023 Digestive Disease Week® (DDW) Shark Tank pitch competition.

Four other finalists

The choice that received the most votes from the audience was Ezalife’s Button Huggie, a device for securing gastrostomy and cecostomy buttons. It includes a reusable, child-proof lid with a disposable, biodegradable, gauze sponge and a base layer held in place with a long-wearing adhesive. This prevents button movement in the tract, which can delay wound healing and lead to complications. In addition, the Button Huggie is much easier to put in place. “Our device is novel, with no direct competitors,” said CTO/COO Tyler Mironuck.

Currently patients are advised to fasten gastrostomy and cecostomy buttons with tape, but the buttons are dislodged 7% of the time, he said. The company estimates that patients spend an average of $100 a month on tape and gauze. The Button Huggie can be manufactured for $56, and the company envisions selling them for $300.

The device is exempt from needing a 510K FDA approval, so it can get to the market quickly. Nevertheless, the company is conducting a clinical trial with 200 patients at five children’s hospitals, Mr. Mironuck said.

NovaScan was a finalist for nsCanary, a device that uses electrical impedance to detect cancer. The device hinges on the company’s discovery that the Cole relaxation frequency is orders of magnitude different for cancerous and benign tissue, yet not affected by mass. By measuring this frequency, the nsCanary can find cancer in tissue acquired through biopsy forceps, snare polypectomy, mucosal resection, and endoscopic ultrasound-guided fine needle biopsy. It works in seconds without the need to interpret images.

Atlas Endoscopy was recognized for REN, a robotic colonoscopy system. The operator uses an external actuating magnet above the patient to guide a disposable ultracompliant endoscope through the colon. The company says this form of navigation prevents looping, reduces pain, and minimizes tissue stress.

Limaca Medical was recognized for Precision, a motorized, automated, rotational cutting and coring needle for endoscopic ultrasound biopsy. Manual biopsy needles now on the market require repeat passes in and out of the endoscope to obtain fragments of tissue, but Precision obtains larger intact samples of tumor tissue in a single pass.

Dr. Sethi has served as a consultant for Boston Scientific, Medtronic and Olympus; as a board member for EndoSound and has received grant support from FUJIFILM.
 

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.

The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.

Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.

The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
 

Improving a ‘specific and fundamental’ feature of HFpEF

“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.

However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.

“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.

He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.

“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
 

An ‘obese, cardiometabolic’ HFpEF phenotype

The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.

Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.

An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.

The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.

The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.

NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.

The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.

Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.

The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
 

Improving a ‘specific and fundamental’ feature of HFpEF

“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.

However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.

“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.

He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.

“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
 

An ‘obese, cardiometabolic’ HFpEF phenotype

The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.

Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.

An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.

The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.

The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.

NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.

The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.

Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.

The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
 

Improving a ‘specific and fundamental’ feature of HFpEF

“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.

However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.

“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.

He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.

“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
 

An ‘obese, cardiometabolic’ HFpEF phenotype

The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.

Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.

An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.

The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.

The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.

NEW ORLEANS – Don’t treat suspected cases of onychomycosis before confirming the diagnosis with a laboratory test, Boni E. Elewski, MD, advises.

“The PAS [periodic acid-Schiff] stain is very popular because it can identify the presence or absence of fungal elements, but a fungal culture will identify the organism living in the nail,” Dr. Elewski, professor and chair of dermatology at the University of Alabama, Birmingham, said at the annual meeting of the American Academy of Dermatology. “You also could do a PCR to identify the organism, with or without a KOH or PAS stain. It is often helpful to know what organism is causing the infection.”

University of Alabama, Birmingham

While waiting for lab results, there are three clinical clues to look for – the first being that an infection likely resides in the toenail. “You almost never see dermatophyte onychomycosis in the fingernails without it being in the toenails, too,” Dr. Elewski said.

The presence of tinea pedis is a second clinical clue. “Sometimes it’s subtle, so I will ask the patient, ‘Have you been treating yourself for athlete’s foot?’ If they say ‘no, I’ve never had it,’ put down on your list that it’s unlikely they have onychomycosis. How is the fungus going to jump from the floor into the nail without taking a little vacation on the bottom of the foot? It just isn’t going to happen.”

The presence of dermatophytoma is the third clinical clue. “These are dermatophyte abscesses encased in a biofilm, and they’re really hard to treat,” she said.

Treatments

Clinicians typically turn to one of three oral drugs for treating onychomycosis: terbinafine, itraconazole, and fluconazole, Dr. Elewski noted. Referring to terbinafine as “the gold standard,” she said that she typically writes a prescription for 90 250-mg pills. “When I give terbinafine, I often do baseline liver profiling, depending on the patient’s age, their state of health, their comorbidities, and other medications they’re taking,” she said. “If they’re 18 years old and otherwise healthy, I probably don’t.” While she generally prescribes 90 pills, she added, “keep in mind that 90 pills are not going to cure everybody. I see the patient 4 months later because the drug should stay in the nail for 30 days or more at therapeutic levels after you take that 90-day course.”

Another option is itraconazole, which can be taken at a dose of 200 mg a day for 12 weeks, or at a pulse dose, where patients take 400 mg every day for 1 week, 1 week a month, for 4 consecutive months. “I’ll often do a baseline liver profile with itraconazole, too,” Dr. Elewski said. “I don’t think you have to, but it makes sense if it’s feasible for you. Decide that based on each patient.”

Itraconazole can’t be given concomitantly with statins because of the potential for rhabdomyolysis. For patients taking statins, she consults with their physicians to make sure it’s safe to stop the statin a couple of days before and after their scheduled pulse dose of itraconazole. “This involves 1 week per month of taking itraconazole without the statin,” she said. “Or they could stop statins for the time you treat, if cleared by their doctor.”

As for fluconazole, Dr. Elewski usually prescribes 200 mg once or twice per week until the nail is normal. She offers patients the mnemonic for “Fungal Fridays” or Toesdays” as a way for them to remember which day to take the fluconazole.

According to data in the package inserts, rates of complete and mycologic cures are 38% and 70% for terbinafine, respectively, 14% and 54% for itraconazole, and 37% to 48% and 47% to 62% for fluconazole. “These cures are not 100% based on the standard course [of the drug],” Dr. Elewski noted. “I don’t use the standard course. I believe in treating to terminate. You want to kill the fungus.”
 

Resistant dermatophytes ‘are coming’

Halting treatment with an oral drug at a particular time point instead of when the nail is fungal-free likely contributes to resistant strains, she added, noting that she has at least two dozen patients in her practice with dermatophyte resistance documented in labs. “We need to be antifungal stewards, because resistant dermatophytes are coming to us,” she said. “They’re here already, and we don’t want it to be endemic in the U.S.”

In a published study from 2020, researchers from India enrolled 200 patients with relapsing tinea corporis, tinea cruris, and tinea faciei and allocated 50 each to treatment with either fluconazole, griseofulvin, itraconazole, or terbinafine. At week 4, all treatment arms had cure rates of less than 8%. At week 8, the cure rates were 42% for fluconazole, 16% for griseofulvin, 28% for terbinafine, and 66% for itraconazole.

Based in part on these study findings, Dr. Elewski said that she has become more aggressive in her therapeutic approach, including treating some of her patients on terbinafine for a minimum of 6 months. “If that’s not enough, I keep treating,” she said. “But, patients may not respond to terbinafine; we see resistance. So, itraconazole may be our best drug going forward for treating onychomycosis. You just have to watch out for side effects of itraconazole, mainly drug-drug interactions.”

Dr. Elewski reported having no relevant financial disclosures related to her presentation.

NEW ORLEANS – Don’t treat suspected cases of onychomycosis before confirming the diagnosis with a laboratory test, Boni E. Elewski, MD, advises.

“The PAS [periodic acid-Schiff] stain is very popular because it can identify the presence or absence of fungal elements, but a fungal culture will identify the organism living in the nail,” Dr. Elewski, professor and chair of dermatology at the University of Alabama, Birmingham, said at the annual meeting of the American Academy of Dermatology. “You also could do a PCR to identify the organism, with or without a KOH or PAS stain. It is often helpful to know what organism is causing the infection.”

University of Alabama, Birmingham

While waiting for lab results, there are three clinical clues to look for – the first being that an infection likely resides in the toenail. “You almost never see dermatophyte onychomycosis in the fingernails without it being in the toenails, too,” Dr. Elewski said.

The presence of tinea pedis is a second clinical clue. “Sometimes it’s subtle, so I will ask the patient, ‘Have you been treating yourself for athlete’s foot?’ If they say ‘no, I’ve never had it,’ put down on your list that it’s unlikely they have onychomycosis. How is the fungus going to jump from the floor into the nail without taking a little vacation on the bottom of the foot? It just isn’t going to happen.”

The presence of dermatophytoma is the third clinical clue. “These are dermatophyte abscesses encased in a biofilm, and they’re really hard to treat,” she said.

Treatments

Clinicians typically turn to one of three oral drugs for treating onychomycosis: terbinafine, itraconazole, and fluconazole, Dr. Elewski noted. Referring to terbinafine as “the gold standard,” she said that she typically writes a prescription for 90 250-mg pills. “When I give terbinafine, I often do baseline liver profiling, depending on the patient’s age, their state of health, their comorbidities, and other medications they’re taking,” she said. “If they’re 18 years old and otherwise healthy, I probably don’t.” While she generally prescribes 90 pills, she added, “keep in mind that 90 pills are not going to cure everybody. I see the patient 4 months later because the drug should stay in the nail for 30 days or more at therapeutic levels after you take that 90-day course.”

Another option is itraconazole, which can be taken at a dose of 200 mg a day for 12 weeks, or at a pulse dose, where patients take 400 mg every day for 1 week, 1 week a month, for 4 consecutive months. “I’ll often do a baseline liver profile with itraconazole, too,” Dr. Elewski said. “I don’t think you have to, but it makes sense if it’s feasible for you. Decide that based on each patient.”

Itraconazole can’t be given concomitantly with statins because of the potential for rhabdomyolysis. For patients taking statins, she consults with their physicians to make sure it’s safe to stop the statin a couple of days before and after their scheduled pulse dose of itraconazole. “This involves 1 week per month of taking itraconazole without the statin,” she said. “Or they could stop statins for the time you treat, if cleared by their doctor.”

As for fluconazole, Dr. Elewski usually prescribes 200 mg once or twice per week until the nail is normal. She offers patients the mnemonic for “Fungal Fridays” or Toesdays” as a way for them to remember which day to take the fluconazole.

According to data in the package inserts, rates of complete and mycologic cures are 38% and 70% for terbinafine, respectively, 14% and 54% for itraconazole, and 37% to 48% and 47% to 62% for fluconazole. “These cures are not 100% based on the standard course [of the drug],” Dr. Elewski noted. “I don’t use the standard course. I believe in treating to terminate. You want to kill the fungus.”
 

Resistant dermatophytes ‘are coming’

Halting treatment with an oral drug at a particular time point instead of when the nail is fungal-free likely contributes to resistant strains, she added, noting that she has at least two dozen patients in her practice with dermatophyte resistance documented in labs. “We need to be antifungal stewards, because resistant dermatophytes are coming to us,” she said. “They’re here already, and we don’t want it to be endemic in the U.S.”

In a published study from 2020, researchers from India enrolled 200 patients with relapsing tinea corporis, tinea cruris, and tinea faciei and allocated 50 each to treatment with either fluconazole, griseofulvin, itraconazole, or terbinafine. At week 4, all treatment arms had cure rates of less than 8%. At week 8, the cure rates were 42% for fluconazole, 16% for griseofulvin, 28% for terbinafine, and 66% for itraconazole.

Based in part on these study findings, Dr. Elewski said that she has become more aggressive in her therapeutic approach, including treating some of her patients on terbinafine for a minimum of 6 months. “If that’s not enough, I keep treating,” she said. “But, patients may not respond to terbinafine; we see resistance. So, itraconazole may be our best drug going forward for treating onychomycosis. You just have to watch out for side effects of itraconazole, mainly drug-drug interactions.”

Dr. Elewski reported having no relevant financial disclosures related to her presentation.

NEW ORLEANS – Don’t treat suspected cases of onychomycosis before confirming the diagnosis with a laboratory test, Boni E. Elewski, MD, advises.

“The PAS [periodic acid-Schiff] stain is very popular because it can identify the presence or absence of fungal elements, but a fungal culture will identify the organism living in the nail,” Dr. Elewski, professor and chair of dermatology at the University of Alabama, Birmingham, said at the annual meeting of the American Academy of Dermatology. “You also could do a PCR to identify the organism, with or without a KOH or PAS stain. It is often helpful to know what organism is causing the infection.”

University of Alabama, Birmingham

While waiting for lab results, there are three clinical clues to look for – the first being that an infection likely resides in the toenail. “You almost never see dermatophyte onychomycosis in the fingernails without it being in the toenails, too,” Dr. Elewski said.

The presence of tinea pedis is a second clinical clue. “Sometimes it’s subtle, so I will ask the patient, ‘Have you been treating yourself for athlete’s foot?’ If they say ‘no, I’ve never had it,’ put down on your list that it’s unlikely they have onychomycosis. How is the fungus going to jump from the floor into the nail without taking a little vacation on the bottom of the foot? It just isn’t going to happen.”

The presence of dermatophytoma is the third clinical clue. “These are dermatophyte abscesses encased in a biofilm, and they’re really hard to treat,” she said.

Treatments

Clinicians typically turn to one of three oral drugs for treating onychomycosis: terbinafine, itraconazole, and fluconazole, Dr. Elewski noted. Referring to terbinafine as “the gold standard,” she said that she typically writes a prescription for 90 250-mg pills. “When I give terbinafine, I often do baseline liver profiling, depending on the patient’s age, their state of health, their comorbidities, and other medications they’re taking,” she said. “If they’re 18 years old and otherwise healthy, I probably don’t.” While she generally prescribes 90 pills, she added, “keep in mind that 90 pills are not going to cure everybody. I see the patient 4 months later because the drug should stay in the nail for 30 days or more at therapeutic levels after you take that 90-day course.”

Another option is itraconazole, which can be taken at a dose of 200 mg a day for 12 weeks, or at a pulse dose, where patients take 400 mg every day for 1 week, 1 week a month, for 4 consecutive months. “I’ll often do a baseline liver profile with itraconazole, too,” Dr. Elewski said. “I don’t think you have to, but it makes sense if it’s feasible for you. Decide that based on each patient.”

Itraconazole can’t be given concomitantly with statins because of the potential for rhabdomyolysis. For patients taking statins, she consults with their physicians to make sure it’s safe to stop the statin a couple of days before and after their scheduled pulse dose of itraconazole. “This involves 1 week per month of taking itraconazole without the statin,” she said. “Or they could stop statins for the time you treat, if cleared by their doctor.”

As for fluconazole, Dr. Elewski usually prescribes 200 mg once or twice per week until the nail is normal. She offers patients the mnemonic for “Fungal Fridays” or Toesdays” as a way for them to remember which day to take the fluconazole.

According to data in the package inserts, rates of complete and mycologic cures are 38% and 70% for terbinafine, respectively, 14% and 54% for itraconazole, and 37% to 48% and 47% to 62% for fluconazole. “These cures are not 100% based on the standard course [of the drug],” Dr. Elewski noted. “I don’t use the standard course. I believe in treating to terminate. You want to kill the fungus.”
 

Resistant dermatophytes ‘are coming’

Halting treatment with an oral drug at a particular time point instead of when the nail is fungal-free likely contributes to resistant strains, she added, noting that she has at least two dozen patients in her practice with dermatophyte resistance documented in labs. “We need to be antifungal stewards, because resistant dermatophytes are coming to us,” she said. “They’re here already, and we don’t want it to be endemic in the U.S.”

In a published study from 2020, researchers from India enrolled 200 patients with relapsing tinea corporis, tinea cruris, and tinea faciei and allocated 50 each to treatment with either fluconazole, griseofulvin, itraconazole, or terbinafine. At week 4, all treatment arms had cure rates of less than 8%. At week 8, the cure rates were 42% for fluconazole, 16% for griseofulvin, 28% for terbinafine, and 66% for itraconazole.

Based in part on these study findings, Dr. Elewski said that she has become more aggressive in her therapeutic approach, including treating some of her patients on terbinafine for a minimum of 6 months. “If that’s not enough, I keep treating,” she said. “But, patients may not respond to terbinafine; we see resistance. So, itraconazole may be our best drug going forward for treating onychomycosis. You just have to watch out for side effects of itraconazole, mainly drug-drug interactions.”

Dr. Elewski reported having no relevant financial disclosures related to her presentation.

SAN FRANCISCO – Gastroenterologists are uniquely positioned to treat obesity, according to a panel of experts convened by the American Gastroenterological Association.

“We see this as a field that GI should own,” said Naresh T. Gunaratnam, MD, a gastroenterologist at Huron Gastro in Ypsilanti, Mich., who has made obesity treatment an important part of his practice.

Gastroenterologists are uniquely qualified in endoscopic sleeve gastroplasty and in the placement of intragastric balloons and can also bring their internal medicine training to bear in patient education and medical prescription, Dr. Gunaratnam said in an interview.

He and three colleagues spoke about innovation in obesity and metabolism at the 2023 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

Significant hurdles remain to launching new endoscopic devices for treating obesity, but evidence shows that the existing treatments are effective when combined with medication and other treatments, said panelist Reem Z. Sharaiha, MD, MSc, a gastroenterologist with expertise in obesity at Weill Cornell Medicine in New York. “You can never find just one cure for obesity, you should always think about a combination.”

Obesity rates continue to spiral worldwide, with over 100 million adults in the United States weighing in at over 30 kg/m², said Dr. Sharaiha, but less than 5% per year receive adequate treatment. The condition is driving upticks in diabetes and nonalcoholic fatty liver disease and contributing to cancer, heart disease, stroke, and COVID-19 infections.

Even small reductions in body weight can significantly improve these conditions, she said. Less than a 5% in total body weight on average results in significant reductions in HbA1c, triglycerides, blood pressure and steatosis.

In recent years, the Food and Drug Administration has several devices that gastroenterologists can use to treat obesity, Dr. Sharaiha said, including three brands of intragastric balloon used to reduce appetite by filling the stomach. The AGA now recommends such an intragastric balloon for people with obesity who have “failed a trial of conventional weight-loss strategies.”

But many devices have been withdrawn from the market, including two of the balloon systems. Why do so many devices fail? Sometimes the FDA demands trials that are too expensive, Dr. Sharaiha said. The COVID-19 pandemic put financial pressure on some companies that have already secured FDA approval. Some insurance companies are not willing to pay for the devices, even after the FDA has approved them. Some are not cost effective.

And sometimes patients don’t accept them. That may have been one challenge with Aspire’s AspireAssist, which allowed patients to empty their stomachs into the toilet using a surgically implanted tube, though the company cited “the financial impact of the COVID-19 pandemic” when it withdrew the device from the market last year.

More devices are in the pipeline, but they face an uncertain path forward, Dr. Sharaiha said. “Device companies are usually startups that need funding. With the economic downturn, venture capital funding is hard to get.”

In the meantime, patients with class 3 obesity in particular may benefit from surgery, she said.

For others, medications are playing a more important role in the obesity epidemic, with an average 10%-15% body weight loss, Dr. Sharaiha said. Injections with semaglutide (Ozempic), a glucagon-like peptide 1 (GLP-1) receptor agonist that is approved to improve glycemic control in adults with type 2 diabetes mellitus, is leading the charge.

Tirzepatide (Mounjaro) may be even more effective, Dr. Sharaiha said. The FDA approved the drug last year to improve blood sugar control in adults with type 2 diabetes and was fast-tracked in October for the treatment of adults with obesity, or who are overweight with weight-related comorbidities.

Medications provide add-on benefits to many patients who have been treated with intragastric balloons or endoscopic sleeve gastroplasty, Dr. Sharaiha said.

Also lifestyle and education should not be neglected, said Dr. Gunaratnam, who lost 50 pounds by changing his diet. He urged gastroenterologists to take on the challenge of treating obesity. It’s not the part of his practice with the best reimbursement, but it is the most satisfying. “I get more hugs, cards, and tears by doing this because when you change weight, you’re impacting every part of their lives,” he said.

Dr. Gunaratnam is the founder of Lean Medical LLC and Satya Health Sciences. Dr. Sharaiha has served as a consultant for Boston Scientific Corporation and Cook Medical Inc.

SAN FRANCISCO – Gastroenterologists are uniquely positioned to treat obesity, according to a panel of experts convened by the American Gastroenterological Association.

“We see this as a field that GI should own,” said Naresh T. Gunaratnam, MD, a gastroenterologist at Huron Gastro in Ypsilanti, Mich., who has made obesity treatment an important part of his practice.

Gastroenterologists are uniquely qualified in endoscopic sleeve gastroplasty and in the placement of intragastric balloons and can also bring their internal medicine training to bear in patient education and medical prescription, Dr. Gunaratnam said in an interview.

He and three colleagues spoke about innovation in obesity and metabolism at the 2023 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

Significant hurdles remain to launching new endoscopic devices for treating obesity, but evidence shows that the existing treatments are effective when combined with medication and other treatments, said panelist Reem Z. Sharaiha, MD, MSc, a gastroenterologist with expertise in obesity at Weill Cornell Medicine in New York. “You can never find just one cure for obesity, you should always think about a combination.”

Obesity rates continue to spiral worldwide, with over 100 million adults in the United States weighing in at over 30 kg/m², said Dr. Sharaiha, but less than 5% per year receive adequate treatment. The condition is driving upticks in diabetes and nonalcoholic fatty liver disease and contributing to cancer, heart disease, stroke, and COVID-19 infections.

Even small reductions in body weight can significantly improve these conditions, she said. Less than a 5% in total body weight on average results in significant reductions in HbA1c, triglycerides, blood pressure and steatosis.

In recent years, the Food and Drug Administration has several devices that gastroenterologists can use to treat obesity, Dr. Sharaiha said, including three brands of intragastric balloon used to reduce appetite by filling the stomach. The AGA now recommends such an intragastric balloon for people with obesity who have “failed a trial of conventional weight-loss strategies.”

But many devices have been withdrawn from the market, including two of the balloon systems. Why do so many devices fail? Sometimes the FDA demands trials that are too expensive, Dr. Sharaiha said. The COVID-19 pandemic put financial pressure on some companies that have already secured FDA approval. Some insurance companies are not willing to pay for the devices, even after the FDA has approved them. Some are not cost effective.

And sometimes patients don’t accept them. That may have been one challenge with Aspire’s AspireAssist, which allowed patients to empty their stomachs into the toilet using a surgically implanted tube, though the company cited “the financial impact of the COVID-19 pandemic” when it withdrew the device from the market last year.

More devices are in the pipeline, but they face an uncertain path forward, Dr. Sharaiha said. “Device companies are usually startups that need funding. With the economic downturn, venture capital funding is hard to get.”

In the meantime, patients with class 3 obesity in particular may benefit from surgery, she said.

For others, medications are playing a more important role in the obesity epidemic, with an average 10%-15% body weight loss, Dr. Sharaiha said. Injections with semaglutide (Ozempic), a glucagon-like peptide 1 (GLP-1) receptor agonist that is approved to improve glycemic control in adults with type 2 diabetes mellitus, is leading the charge.

Tirzepatide (Mounjaro) may be even more effective, Dr. Sharaiha said. The FDA approved the drug last year to improve blood sugar control in adults with type 2 diabetes and was fast-tracked in October for the treatment of adults with obesity, or who are overweight with weight-related comorbidities.

Medications provide add-on benefits to many patients who have been treated with intragastric balloons or endoscopic sleeve gastroplasty, Dr. Sharaiha said.

Also lifestyle and education should not be neglected, said Dr. Gunaratnam, who lost 50 pounds by changing his diet. He urged gastroenterologists to take on the challenge of treating obesity. It’s not the part of his practice with the best reimbursement, but it is the most satisfying. “I get more hugs, cards, and tears by doing this because when you change weight, you’re impacting every part of their lives,” he said.

Dr. Gunaratnam is the founder of Lean Medical LLC and Satya Health Sciences. Dr. Sharaiha has served as a consultant for Boston Scientific Corporation and Cook Medical Inc.

SAN FRANCISCO – Gastroenterologists are uniquely positioned to treat obesity, according to a panel of experts convened by the American Gastroenterological Association.

“We see this as a field that GI should own,” said Naresh T. Gunaratnam, MD, a gastroenterologist at Huron Gastro in Ypsilanti, Mich., who has made obesity treatment an important part of his practice.

Gastroenterologists are uniquely qualified in endoscopic sleeve gastroplasty and in the placement of intragastric balloons and can also bring their internal medicine training to bear in patient education and medical prescription, Dr. Gunaratnam said in an interview.

He and three colleagues spoke about innovation in obesity and metabolism at the 2023 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

Significant hurdles remain to launching new endoscopic devices for treating obesity, but evidence shows that the existing treatments are effective when combined with medication and other treatments, said panelist Reem Z. Sharaiha, MD, MSc, a gastroenterologist with expertise in obesity at Weill Cornell Medicine in New York. “You can never find just one cure for obesity, you should always think about a combination.”

Obesity rates continue to spiral worldwide, with over 100 million adults in the United States weighing in at over 30 kg/m², said Dr. Sharaiha, but less than 5% per year receive adequate treatment. The condition is driving upticks in diabetes and nonalcoholic fatty liver disease and contributing to cancer, heart disease, stroke, and COVID-19 infections.

Even small reductions in body weight can significantly improve these conditions, she said. Less than a 5% in total body weight on average results in significant reductions in HbA1c, triglycerides, blood pressure and steatosis.

In recent years, the Food and Drug Administration has several devices that gastroenterologists can use to treat obesity, Dr. Sharaiha said, including three brands of intragastric balloon used to reduce appetite by filling the stomach. The AGA now recommends such an intragastric balloon for people with obesity who have “failed a trial of conventional weight-loss strategies.”

But many devices have been withdrawn from the market, including two of the balloon systems. Why do so many devices fail? Sometimes the FDA demands trials that are too expensive, Dr. Sharaiha said. The COVID-19 pandemic put financial pressure on some companies that have already secured FDA approval. Some insurance companies are not willing to pay for the devices, even after the FDA has approved them. Some are not cost effective.

And sometimes patients don’t accept them. That may have been one challenge with Aspire’s AspireAssist, which allowed patients to empty their stomachs into the toilet using a surgically implanted tube, though the company cited “the financial impact of the COVID-19 pandemic” when it withdrew the device from the market last year.

More devices are in the pipeline, but they face an uncertain path forward, Dr. Sharaiha said. “Device companies are usually startups that need funding. With the economic downturn, venture capital funding is hard to get.”

In the meantime, patients with class 3 obesity in particular may benefit from surgery, she said.

For others, medications are playing a more important role in the obesity epidemic, with an average 10%-15% body weight loss, Dr. Sharaiha said. Injections with semaglutide (Ozempic), a glucagon-like peptide 1 (GLP-1) receptor agonist that is approved to improve glycemic control in adults with type 2 diabetes mellitus, is leading the charge.

Tirzepatide (Mounjaro) may be even more effective, Dr. Sharaiha said. The FDA approved the drug last year to improve blood sugar control in adults with type 2 diabetes and was fast-tracked in October for the treatment of adults with obesity, or who are overweight with weight-related comorbidities.

Medications provide add-on benefits to many patients who have been treated with intragastric balloons or endoscopic sleeve gastroplasty, Dr. Sharaiha said.

Also lifestyle and education should not be neglected, said Dr. Gunaratnam, who lost 50 pounds by changing his diet. He urged gastroenterologists to take on the challenge of treating obesity. It’s not the part of his practice with the best reimbursement, but it is the most satisfying. “I get more hugs, cards, and tears by doing this because when you change weight, you’re impacting every part of their lives,” he said.

Dr. Gunaratnam is the founder of Lean Medical LLC and Satya Health Sciences. Dr. Sharaiha has served as a consultant for Boston Scientific Corporation and Cook Medical Inc.

WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.

In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Ted Bosworth/MDedge News

In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.

Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
 

No surprises found in real-world outcome

At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.

By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.

At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.

Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.

When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.

In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.

Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.

The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.

“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
 

Elderly patients benefit equally from Watchman

Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.

To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.

In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.

“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.

In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.

Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
 

ESRD is not Watchman contraindication

A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.

Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.

Ted Bosworth/MDedge News

WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.

In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Ted Bosworth/MDedge News

In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.

Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
 

No surprises found in real-world outcome

At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.

By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.

At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.

Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.

When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.

In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.

Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.

The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.

“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
 

Elderly patients benefit equally from Watchman

Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.

To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.

In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.

“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.

In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.

Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
 

ESRD is not Watchman contraindication

A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.

Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.

Ted Bosworth/MDedge News

WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.

In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Ted Bosworth/MDedge News

In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.

Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
 

No surprises found in real-world outcome

At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.

By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.

At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.

Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.

When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.

In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.

Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.

The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.

“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
 

Elderly patients benefit equally from Watchman

Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.

To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.

In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.

“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.

In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.

Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
 

ESRD is not Watchman contraindication

A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.

Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.

Ted Bosworth/MDedge News

NEW ORLEANS – Nemolizumab monotherapy for 16 weeks improved itch, skin lesions, and sleep disturbances in adults with prurigo nodularis (PN), results from a phase 3 trial demonstrated.

Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.

After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.

Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.

Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
 

Primary, secondary endpoint results

Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).

As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
 

Adverse events

Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.

The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.

“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”

Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”

Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.

NEW ORLEANS – Nemolizumab monotherapy for 16 weeks improved itch, skin lesions, and sleep disturbances in adults with prurigo nodularis (PN), results from a phase 3 trial demonstrated.

Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.

After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.

Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.

Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
 

Primary, secondary endpoint results

Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).

As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
 

Adverse events

Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.

The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.

“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”

Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”

Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.

NEW ORLEANS – Nemolizumab monotherapy for 16 weeks improved itch, skin lesions, and sleep disturbances in adults with prurigo nodularis (PN), results from a phase 3 trial demonstrated.

Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.

After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.

Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.

Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
 

Primary, secondary endpoint results

Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).

As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
 

Adverse events

Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.

The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.

“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”

Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”

Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.

DENVER – People with lower expectations of how they would be able to use their knees during work activities after a total knee arthroplasty were more dissatisfied with their knee abilities 6 months after their surgery, according to a study presented at the OARSI 2023 World Congress.

Two out of 10 patients are dissatisfied after total knee arthroplasty, which is increasingly performed in younger and working patients who may have higher demands, presenter Yvonne van Zaanen, a physiotherapist in occupational health and ergonomics and a PhD candidate at Amsterdam University Medical Center, told attendees.

The findings suggest a correlation between patients’ low presurgical expectations of their ability to use their knees and having more difficulty with their knees postoperatively, she said. “We should take better care of working patients with low expectations by managing their preoperative expectations and improving their ability to perform work-related knee-straining activities in rehabilitation,” Ms. van Zaanen told attendees.

The researchers conducted a multicenter, prospective cohort study involving seven hospitals. They surveyed 175 employed individuals aged 18-65 years who were scheduled for a total knee arthroplasty and intended to return to work after their surgery. The first survey occurred before the operation, and the follow-up occurred 6 months after the surgery.

Just over half the participants were women (53%), and the average participant age was 59. Respondents had a mean body mass index (BMI) of 29 kg/m², and had a Knee injury and Osteoarthritis Outcome Score (KOOS) pain score of 42 (on a 0-to-100 scale in which lower scores are worse). About half the respondents (51%) had a job that involved knee-straining activities.

The researchers assessed participants’ ability to perform work-related, knee-straining activities using the Work, Osteoarthritis, or joint-Replacement Questionnaire (WORQ) tool, which considers the following activities: kneeling, crouching, clambering, taking the stairs, walking on rough terrain, working with hands below knee height, standing, lifting or carrying, pushing or pulling, walking on ground level, operating a vehicle, operating foot pedals, and sitting. The 0-to-100 scale rates the difficulty of using knees for each particular activity, with higher scores indicating greater ease and less pain in doing that activity.

Among the 107 patients who expected to be satisfied after their surgery, half (n = 53) were satisfied, compared with 12% (n = 13) who were unsatisfied; the remaining participants (n = 41, 38%) were neither satisfied nor dissatisfied. Among the 24 patients who expected to be dissatisfied after their surgery, one-third (n = 8) were satisfied and 42% (n = 10) were dissatisfied. The remaining 44 patients didn’t expect to be satisfied or dissatisfied before their surgery, and 41% of them were satisfied while 23% were dissatisfied.

The researchers found that patients’ expectation of their satisfaction level going into the surgery was the only preoperative factor to be prognostic for dissatisfaction 6 months after surgery, based on their WORQ score. That is, patients who expected to be dissatisfied before their surgery had approximately five times greater odds of being dissatisfied after their surgery than did those who expected to be satisfied with their ability to do knee-straining activities at work (odds ratio, 5.1; 95% confidence interval, 1.7-15.5). Among those with a WORQ score of 40, indicating a greater expectation of difficulty using their knees postoperatively, 55% were dissatisfied after their surgery, compared with 19% of those with a WORQ score of 85, who expected greater knee ability after their surgery.

The other factors that the researchers examined, which had no effect on WORQ scores, included age, sex, BMI, education, comorbidities, KOOS pain subscale, having a knee-straining job, having needed surgery because of work, or having preoperative sick leave.

One discussion prompted by the presentation focused specifically on individuals’ ability to kneel without much difficulty after their surgery, an activity that’s not typically considered likely, Ms. van Zaanen noted. One audience member, Gillian Hawker, MD, MSc, a professor of medicine in the division of rheumatology at the University of Toronto, questioned whether the field should accept that current reality from surgical intervention. Dr. Hawker described a cohort she had analyzed in which two-thirds of the participants had expected they would be able to kneel after their surgery, regardless of whether it was related to work or other activities.

“Kneeling is important, not just for work; it’s important for culture and religion and lots of other things,” Dr. Hawker said. “How will you help these people to kneel after knee replacement when the surgery isn’t really performed to enable people to do that?” In response, Ms. van Zaanen noted it might not be achievable, as the research literature demonstrates, but Dr. Hawker suggested that is itself problematic.

“I guess what I’m asking is, why are we settling for that? If it’s important to so many people, and an expectation of so many people, why don’t we technologically improve such that, post arthroplasty, people can kneel?”

Another commenter suggested that the study’s findings may not indicate a need to manage patients’ expectations prior to surgery so much as showing that some patients simply have realistic expectations of what they will and will not be able to do after knee replacement.

“Is it possible that people who had low expectations – those who expected to be dissatisfied afterwards – were appropriately understanding that they were likely to be dissatisfied afterwards, in which case, managing their expectations might do nothing for their dissatisfaction afterwards?” the commenter asked. It is likely necessary to conduct additional research about expectations before surgery and experiences after surgery to address that question, Ms. van Zaanen suggested.

Ms. van Zaanen and Dr. Hawker reported having no relevant financial relationships. The presentation did not note any external funding. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – People with lower expectations of how they would be able to use their knees during work activities after a total knee arthroplasty were more dissatisfied with their knee abilities 6 months after their surgery, according to a study presented at the OARSI 2023 World Congress.

Two out of 10 patients are dissatisfied after total knee arthroplasty, which is increasingly performed in younger and working patients who may have higher demands, presenter Yvonne van Zaanen, a physiotherapist in occupational health and ergonomics and a PhD candidate at Amsterdam University Medical Center, told attendees.

The findings suggest a correlation between patients’ low presurgical expectations of their ability to use their knees and having more difficulty with their knees postoperatively, she said. “We should take better care of working patients with low expectations by managing their preoperative expectations and improving their ability to perform work-related knee-straining activities in rehabilitation,” Ms. van Zaanen told attendees.

The researchers conducted a multicenter, prospective cohort study involving seven hospitals. They surveyed 175 employed individuals aged 18-65 years who were scheduled for a total knee arthroplasty and intended to return to work after their surgery. The first survey occurred before the operation, and the follow-up occurred 6 months after the surgery.

Just over half the participants were women (53%), and the average participant age was 59. Respondents had a mean body mass index (BMI) of 29 kg/m², and had a Knee injury and Osteoarthritis Outcome Score (KOOS) pain score of 42 (on a 0-to-100 scale in which lower scores are worse). About half the respondents (51%) had a job that involved knee-straining activities.

The researchers assessed participants’ ability to perform work-related, knee-straining activities using the Work, Osteoarthritis, or joint-Replacement Questionnaire (WORQ) tool, which considers the following activities: kneeling, crouching, clambering, taking the stairs, walking on rough terrain, working with hands below knee height, standing, lifting or carrying, pushing or pulling, walking on ground level, operating a vehicle, operating foot pedals, and sitting. The 0-to-100 scale rates the difficulty of using knees for each particular activity, with higher scores indicating greater ease and less pain in doing that activity.

Among the 107 patients who expected to be satisfied after their surgery, half (n = 53) were satisfied, compared with 12% (n = 13) who were unsatisfied; the remaining participants (n = 41, 38%) were neither satisfied nor dissatisfied. Among the 24 patients who expected to be dissatisfied after their surgery, one-third (n = 8) were satisfied and 42% (n = 10) were dissatisfied. The remaining 44 patients didn’t expect to be satisfied or dissatisfied before their surgery, and 41% of them were satisfied while 23% were dissatisfied.

The researchers found that patients’ expectation of their satisfaction level going into the surgery was the only preoperative factor to be prognostic for dissatisfaction 6 months after surgery, based on their WORQ score. That is, patients who expected to be dissatisfied before their surgery had approximately five times greater odds of being dissatisfied after their surgery than did those who expected to be satisfied with their ability to do knee-straining activities at work (odds ratio, 5.1; 95% confidence interval, 1.7-15.5). Among those with a WORQ score of 40, indicating a greater expectation of difficulty using their knees postoperatively, 55% were dissatisfied after their surgery, compared with 19% of those with a WORQ score of 85, who expected greater knee ability after their surgery.

The other factors that the researchers examined, which had no effect on WORQ scores, included age, sex, BMI, education, comorbidities, KOOS pain subscale, having a knee-straining job, having needed surgery because of work, or having preoperative sick leave.

One discussion prompted by the presentation focused specifically on individuals’ ability to kneel without much difficulty after their surgery, an activity that’s not typically considered likely, Ms. van Zaanen noted. One audience member, Gillian Hawker, MD, MSc, a professor of medicine in the division of rheumatology at the University of Toronto, questioned whether the field should accept that current reality from surgical intervention. Dr. Hawker described a cohort she had analyzed in which two-thirds of the participants had expected they would be able to kneel after their surgery, regardless of whether it was related to work or other activities.

“Kneeling is important, not just for work; it’s important for culture and religion and lots of other things,” Dr. Hawker said. “How will you help these people to kneel after knee replacement when the surgery isn’t really performed to enable people to do that?” In response, Ms. van Zaanen noted it might not be achievable, as the research literature demonstrates, but Dr. Hawker suggested that is itself problematic.

“I guess what I’m asking is, why are we settling for that? If it’s important to so many people, and an expectation of so many people, why don’t we technologically improve such that, post arthroplasty, people can kneel?”

Another commenter suggested that the study’s findings may not indicate a need to manage patients’ expectations prior to surgery so much as showing that some patients simply have realistic expectations of what they will and will not be able to do after knee replacement.

“Is it possible that people who had low expectations – those who expected to be dissatisfied afterwards – were appropriately understanding that they were likely to be dissatisfied afterwards, in which case, managing their expectations might do nothing for their dissatisfaction afterwards?” the commenter asked. It is likely necessary to conduct additional research about expectations before surgery and experiences after surgery to address that question, Ms. van Zaanen suggested.

Ms. van Zaanen and Dr. Hawker reported having no relevant financial relationships. The presentation did not note any external funding. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – People with lower expectations of how they would be able to use their knees during work activities after a total knee arthroplasty were more dissatisfied with their knee abilities 6 months after their surgery, according to a study presented at the OARSI 2023 World Congress.

Two out of 10 patients are dissatisfied after total knee arthroplasty, which is increasingly performed in younger and working patients who may have higher demands, presenter Yvonne van Zaanen, a physiotherapist in occupational health and ergonomics and a PhD candidate at Amsterdam University Medical Center, told attendees.

The findings suggest a correlation between patients’ low presurgical expectations of their ability to use their knees and having more difficulty with their knees postoperatively, she said. “We should take better care of working patients with low expectations by managing their preoperative expectations and improving their ability to perform work-related knee-straining activities in rehabilitation,” Ms. van Zaanen told attendees.

The researchers conducted a multicenter, prospective cohort study involving seven hospitals. They surveyed 175 employed individuals aged 18-65 years who were scheduled for a total knee arthroplasty and intended to return to work after their surgery. The first survey occurred before the operation, and the follow-up occurred 6 months after the surgery.

Just over half the participants were women (53%), and the average participant age was 59. Respondents had a mean body mass index (BMI) of 29 kg/m², and had a Knee injury and Osteoarthritis Outcome Score (KOOS) pain score of 42 (on a 0-to-100 scale in which lower scores are worse). About half the respondents (51%) had a job that involved knee-straining activities.

The researchers assessed participants’ ability to perform work-related, knee-straining activities using the Work, Osteoarthritis, or joint-Replacement Questionnaire (WORQ) tool, which considers the following activities: kneeling, crouching, clambering, taking the stairs, walking on rough terrain, working with hands below knee height, standing, lifting or carrying, pushing or pulling, walking on ground level, operating a vehicle, operating foot pedals, and sitting. The 0-to-100 scale rates the difficulty of using knees for each particular activity, with higher scores indicating greater ease and less pain in doing that activity.

Among the 107 patients who expected to be satisfied after their surgery, half (n = 53) were satisfied, compared with 12% (n = 13) who were unsatisfied; the remaining participants (n = 41, 38%) were neither satisfied nor dissatisfied. Among the 24 patients who expected to be dissatisfied after their surgery, one-third (n = 8) were satisfied and 42% (n = 10) were dissatisfied. The remaining 44 patients didn’t expect to be satisfied or dissatisfied before their surgery, and 41% of them were satisfied while 23% were dissatisfied.

The researchers found that patients’ expectation of their satisfaction level going into the surgery was the only preoperative factor to be prognostic for dissatisfaction 6 months after surgery, based on their WORQ score. That is, patients who expected to be dissatisfied before their surgery had approximately five times greater odds of being dissatisfied after their surgery than did those who expected to be satisfied with their ability to do knee-straining activities at work (odds ratio, 5.1; 95% confidence interval, 1.7-15.5). Among those with a WORQ score of 40, indicating a greater expectation of difficulty using their knees postoperatively, 55% were dissatisfied after their surgery, compared with 19% of those with a WORQ score of 85, who expected greater knee ability after their surgery.

The other factors that the researchers examined, which had no effect on WORQ scores, included age, sex, BMI, education, comorbidities, KOOS pain subscale, having a knee-straining job, having needed surgery because of work, or having preoperative sick leave.

One discussion prompted by the presentation focused specifically on individuals’ ability to kneel without much difficulty after their surgery, an activity that’s not typically considered likely, Ms. van Zaanen noted. One audience member, Gillian Hawker, MD, MSc, a professor of medicine in the division of rheumatology at the University of Toronto, questioned whether the field should accept that current reality from surgical intervention. Dr. Hawker described a cohort she had analyzed in which two-thirds of the participants had expected they would be able to kneel after their surgery, regardless of whether it was related to work or other activities.

“Kneeling is important, not just for work; it’s important for culture and religion and lots of other things,” Dr. Hawker said. “How will you help these people to kneel after knee replacement when the surgery isn’t really performed to enable people to do that?” In response, Ms. van Zaanen noted it might not be achievable, as the research literature demonstrates, but Dr. Hawker suggested that is itself problematic.

“I guess what I’m asking is, why are we settling for that? If it’s important to so many people, and an expectation of so many people, why don’t we technologically improve such that, post arthroplasty, people can kneel?”

Another commenter suggested that the study’s findings may not indicate a need to manage patients’ expectations prior to surgery so much as showing that some patients simply have realistic expectations of what they will and will not be able to do after knee replacement.

“Is it possible that people who had low expectations – those who expected to be dissatisfied afterwards – were appropriately understanding that they were likely to be dissatisfied afterwards, in which case, managing their expectations might do nothing for their dissatisfaction afterwards?” the commenter asked. It is likely necessary to conduct additional research about expectations before surgery and experiences after surgery to address that question, Ms. van Zaanen suggested.

Ms. van Zaanen and Dr. Hawker reported having no relevant financial relationships. The presentation did not note any external funding. The Congress was sponsored by the Osteoarthritis Research Society International.