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The latest results from long-term follow-up of the two trials evaluating transcatheter aortic-valve replacement (TAVR) vs. surgery in patients with low surgical risk have shown different results.

The PARTNER-3 and Evolut trials were heralded as a landmark advance in medicine when the 1-year results from the two studies were presented back in 2019. Both trials suggested benefits of the less-invasive TAVR approach over surgery.

But because these low-surgical-risk patients are younger and will likely have a longer lifespan than will higher risk patients for whom the TAVR technique was first established, patient outcomes and information on how the TAVR devices hold up over the long-term are critical to inform clinical decision-making.

Latest results from the two trials show that the initial benefits of TAVR over surgery seen in PARTNER-3 seem to have attenuated over the longer-term, with main outcomes looking very similar in both groups after 5 years.

However, in the Evolut trial, the early benefit in all-cause mortality or disabling stroke seen in the TAVR group is continuing to increase, with current results showing a 26% relative reduction in this endpoint with TAVR vs. surgery at 4 years.

The 5-year results of the PARTNER-3 trial and the 4-year results of the Evolut study were presented Transcatheter Cardiovascular Therapeutics annual meeting sponsored by the Cardiovascular Research Foundation. Both sets of results were simultaneously published online: PARTNER-3 in The New England Journal of Medicine and Evolut in JACC.

Marty Leon, MD, of NewYork-Presbyterian Columbia University Irving Medical Center, who presented the PARTNER-3 results, said in an interview that both trials are good news for TAVR:

“Both trials have clearly reaffirmed clinical and echocardiographic benefits of TAVR as a meaningful alternative therapy to surgery in low-risk severe symptomatic aortic stenosis patients.” Michael Reardon, MD, Houston Methodist Debakey Heart & Vascular Center, who presented the Evolut results, agreed that both trials were positive for TAVR “as TAVR just has to be as good as surgery to be a winner because clearly it is a lot less invasive.”

But Dr. Dr. Reardon added that, “In making that decision for younger lower-risk patients, then the Evolut valve is the only TAVR valve that has shown superior hemodynamics and durability at all time points with excellent outcomes and widening benefits compared with surgery over the first 4 years.”
 

PARTNER-3

The PARTNER-3 trial randomly assigned 1,000 patients with severe symptomatic aortic stenosis and low surgical risk to undergo either TAVR with the SAPIEN 3 transcatheter heart valve or surgery.

The results at 5 years show no difference in the two primary composite outcomes between TAVR and surgery patients.

The incidence of the composite end point of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure was similar in the TAVR group and the surgery group, occurring in 22.8% of patients in the TAVR group and 27.2% in the surgery group, which is a nonsignificant difference (P = .07).

The incidence of the individual components of the composite end point were also similar in the two groups. Death occurred in 10.0% in the TAVR group and 8.2% in the surgery group; stroke in 5.8% of the TAVR group and 6.4% of the surgery group; and rehospitalization in 13.7% and 17.4%, respectively.

Aortic-valve durability also looked similar in the two groups. The hemodynamic performance of the valve, assessed according to the mean valve gradient, was 12.8 mm Hg in the TAVR group and 11.7 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group.

Among the secondary end points, atrial fibrillation and bleeding appeared to be less frequent in the TAVR group than in the surgery group, whereas paravalvular aortic regurgitation, valve thrombosis, and pacemaker implantation appeared to be less frequent in the surgery group.

Functional and health-status outcomes assessed according to New York Heart Association class, quality of life scores, and the percentage of patients who were alive and well at 5 years appeared to be similar in the two groups.

“These data are reassuring,” Dr. Leon said. “Cardiovascular mortality occurred at a rate of about 1% per year with both therapies, strokes at the rate of 1% per year with both therapies, and hospitalization for cardiovascular reasons at about 3% per year with both therapies. For patients in their 70s, these are very good numbers.”

Along with showing similar outcomes for TAVR and surgery at 5 years, he added, “the need for re-intervention was particularly low (2%-3%) and equivalent for both approaches. And structural valve deterioration was also very low and equivalent in both groups.”
 

Evolut low-risk trial

The Evolut trial enrolled 1,414 patients with low surgical risk who were randomly assigned to TAVR, a self-expanding supra-annular CoreValve Evolut R PRO, or surgery.

By 4 years, the primary endpoint of all-cause mortality or disabling stroke had occurred in 10.7% of the TAVR group and 14.1% in the surgery group (hazard ratio, 0.74; P = .05), representing a 26% relative reduction with TAVR.

The absolute difference between treatment arms for the primary endpoint continued to increase over time: 1.8% at 1 year, 2.0% at 2 years, 2.9% at 3 years, and 3.4% at 4 years.

Rates of the primary endpoint components were all-cause mortality 9.0% with TAVR vs. 12.1% with surgery (P = .07); and disabling stroke was 2.9% with TAVR) vs. 3.8% for surgery (P = .32). Aortic valve rehospitalization was 10.3% with TAVR vs. 12.1% with surgery (P = .27).

The composite of all-cause mortality, disabling stroke, or aortic valve rehospitalization was significantly lower with TAVR, compared with surgery (18.0% vs. 22.4%; HR, 0.78; P = .04).

New permanent pacemaker implantation was significantly higher in the TAVR group (24.6% vs. 9.9%).

Indicators of valve performance including aortic valve reintervention (1.3% TAVR vs. 1.7% surgery); clinical or subclinical valve thrombosis (0.7% TAVR vs. 0.6% surgery); and valve endocarditis (0.9% TAVR vs. 2.2% surgery) were similarly low between groups, the authors report.

TAVR patients had sustained improvement in hemodynamics as measured by echocardiography, with significantly lower aortic valve mean gradients (9.8 mm Hg TAVR vs. 12.1 mm Hg surgery) and greater effective orifice area (2.1 cm² TAVR vs. 2.0 cm² surgery).

At 4 years, 84.7% of TAVR patients and 98.4% of surgery patients had no or trace paravalvular regurgitation, and there was no difference between groups in moderate or greater paravalvular regurgitation (0.4% TAVR vs. 0.0% surgery).

“The Evolut valve has shown a superior performance to surgery,” Dr. Reardon concluded. “It has less structural valve deterioration, less severe patient prosthetic mismatch, and superior hemodynamics, compared to surgery. All these factors are translating into a widening difference in clinical event curves year on year with the Evolut valve vs. surgery.”
 

Why the difference between trials?

The big question is why the early benefit seen with TAVR vs. surgery in both trials was attenuated by 5 years in PARTNER-3 but seemed to become greater each year in the Evolut trial. There were no definite explanations for these observations, but several possibilities were suggested.

Dr. Leon noted that with trials of intervention vs. surgery, it is common for the intervention group to do better in the beginning and for surgery to catch up a bit in later years. “So, it is not that much of a surprise to see outcomes plateauing in PARTNER-3.”

But he also suggested some other factors that may have played a role, one of which was the COVID pandemic.

“During the 2-year COVID period more than 75% of the deaths and strokes in the trial occurred in the TAVR patients,” he said. “Surgery patients were getting more anticoagulation because they had more paroxysmal [atrial fibrillation]. We know that COVID is a stimulus of thrombogenic events so in an odd way we think there may have been some cardioprotective effects from anticoagulation therapy in the surgery group.”

He also pointed out that though hospitalization and strokes were slightly lower with TAVR vs. surgery in the PARTNER-3 trial, mortality was slightly greater in the TAVR group.

“There was a 2:1 ratio in the TAVR and surgery groups in noncardiovascular deaths which influenced the all-cause mortality numbers,” he noted.
 

Mortality rates in the surgery groups

Dr. Leon also pointed out differences in the mortality rates in the surgery groups in the two trials, which he suggested may contribute to the explanation for the different longer-term results.

“The baseline characteristics for patients in these two trials were almost identical, and results at 1 year were very similar, but for whatever reason, over the course of a few years, the outcomes in the Evolut trial were different to those in PARTNER-3, and in particular the difference was in the surgical arms, with a higher event rate in the surgical arm in Evolut than in the surgery arm in PARTNER-3,” he said. “When the control does not perform well it is a lot easier to show that the experimental arm is better.”

“When you look at the TAVR arms in both studies at each time point they are either similar or PARTNER-3 is actually lower,” he added. “That is why it is so difficult to compare these two trials.”

But Dr. Reardon dismissed this argument.

“What determines long-term survival after a procedure is the intrinsic risk level of the patients,” he said. “Overall mortality rates differ between the two trials because the PARTNER-3 trial enrolled a lower end of a low-risk population while Evolut enrolled an upper end of a low-risk population. You cannot look at absolute numbers between trials. That is intellectually and scientifically invalid.”

“It is the relative difference between surgery and TAVR that we are interested in, and we see in Evolut that the relative difference between the two procedures in terms of benefit with TAVR is widening every year,” he added. “That is because the superior valve performance and hemodynamics of the Evolut valve compared to surgery has translated into excellent clinical outcomes.

“In the PARTNER-3 trial – their curves are coming together. I think that is worrisome, but I don’t want to draw conclusions about their trial,” Dr. Reardon said. “All I know is that in our trial, we have excellent outcomes that are getting better year after year.”
 

Competition between valves

The different results of the two trials is inevitably producing some competition between the two products.

Dr. Reardon said: “In terms of which valve to use, clinicians will want to choose a valve that has the best durability and shows the best survival vs. surgery and that is clearly the Evolut valve. I think the writing is on the wall. Some clinicians are going to wait for longer term data, but the question is do we have enough long-term data now.”

But Dr. Leon countered: “There’s never been a head-to-head device to suggest that the self- expanding device performs better than the balloon expanding device. We always think about them as being similar in terms of performance. There is an aggressive effort to suggest that by virtue of the current trial results there was a superior outcome with the Medtronic device, but it’s hard to explain why that would be the case, and we should not compare between the two trials.”

Both Dr. Leon and Dr. Reardon stressed that longer-term follow-up is critical because some surgical valves are known to fail between 5-10 years, and it is not known how the TAVR valves will perform over that period.

Both the PARTNER-3 and Evolut trials are planning to keep following patients out to 10 years.

For the time being though, both Dr. Leon and Dr. Reardon agreed that these current results will probably accelerate the already rapid transition from surgery to TAVR in low-risk patients.

“TAVR will be the default therapy,” Dr. Leon commented. “It will be the first choice for patients. Whether TAVR is superior to surgery in terms of outcomes or just the same, there are sufficient benefits from a logistic and patient perspective that most people would prefer to have the less invasive therapy. TAVR is a one-day procedure, there is no need for general anesthetic, a lot of the secondary outcomes that are so problematic with surgery don’t exist, and the ability to be in a symptom-free state is dramatically accelerated.”

“This was the first serious foray into the low-risk population with TAVR,” he added. “We had an age cut of 65 years, but the vast majority of patients in both trials were over 70. We could now start looking at younger patient populations.”

But Dr. Reardon said that these younger patients are already being given TAVR, and future trials randomizing between TAVR and surgery may not be possible.

“Even though US guidelines still recommend surgery for patients under 65 years, patients want TAVR, and they get TAVR,” he said. “Recent data shows that in 2021, use of TAVR rose to 47.5% in patients under 65 needing isolated aortic valve replacement. That doesn’t meet the guidelines but there’s clearly a big shift going on. These results will just keep that momentum going.”

The PARTNER-3 trial was funded by Edwards Lifesciences. The Evolut study was funded by Medtronic. Dr. Leon reports grant support from Edwards Lifesciences and Medtronic. Dr. Reardon receives research grants from Medtronic.

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

The latest results from long-term follow-up of the two trials evaluating transcatheter aortic-valve replacement (TAVR) vs. surgery in patients with low surgical risk have shown different results.

The PARTNER-3 and Evolut trials were heralded as a landmark advance in medicine when the 1-year results from the two studies were presented back in 2019. Both trials suggested benefits of the less-invasive TAVR approach over surgery.

But because these low-surgical-risk patients are younger and will likely have a longer lifespan than will higher risk patients for whom the TAVR technique was first established, patient outcomes and information on how the TAVR devices hold up over the long-term are critical to inform clinical decision-making.

Latest results from the two trials show that the initial benefits of TAVR over surgery seen in PARTNER-3 seem to have attenuated over the longer-term, with main outcomes looking very similar in both groups after 5 years.

However, in the Evolut trial, the early benefit in all-cause mortality or disabling stroke seen in the TAVR group is continuing to increase, with current results showing a 26% relative reduction in this endpoint with TAVR vs. surgery at 4 years.

The 5-year results of the PARTNER-3 trial and the 4-year results of the Evolut study were presented Transcatheter Cardiovascular Therapeutics annual meeting sponsored by the Cardiovascular Research Foundation. Both sets of results were simultaneously published online: PARTNER-3 in The New England Journal of Medicine and Evolut in JACC.

Marty Leon, MD, of NewYork-Presbyterian Columbia University Irving Medical Center, who presented the PARTNER-3 results, said in an interview that both trials are good news for TAVR:

“Both trials have clearly reaffirmed clinical and echocardiographic benefits of TAVR as a meaningful alternative therapy to surgery in low-risk severe symptomatic aortic stenosis patients.” Michael Reardon, MD, Houston Methodist Debakey Heart & Vascular Center, who presented the Evolut results, agreed that both trials were positive for TAVR “as TAVR just has to be as good as surgery to be a winner because clearly it is a lot less invasive.”

But Dr. Dr. Reardon added that, “In making that decision for younger lower-risk patients, then the Evolut valve is the only TAVR valve that has shown superior hemodynamics and durability at all time points with excellent outcomes and widening benefits compared with surgery over the first 4 years.”
 

PARTNER-3

The PARTNER-3 trial randomly assigned 1,000 patients with severe symptomatic aortic stenosis and low surgical risk to undergo either TAVR with the SAPIEN 3 transcatheter heart valve or surgery.

The results at 5 years show no difference in the two primary composite outcomes between TAVR and surgery patients.

The incidence of the composite end point of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure was similar in the TAVR group and the surgery group, occurring in 22.8% of patients in the TAVR group and 27.2% in the surgery group, which is a nonsignificant difference (P = .07).

The incidence of the individual components of the composite end point were also similar in the two groups. Death occurred in 10.0% in the TAVR group and 8.2% in the surgery group; stroke in 5.8% of the TAVR group and 6.4% of the surgery group; and rehospitalization in 13.7% and 17.4%, respectively.

Aortic-valve durability also looked similar in the two groups. The hemodynamic performance of the valve, assessed according to the mean valve gradient, was 12.8 mm Hg in the TAVR group and 11.7 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group.

Among the secondary end points, atrial fibrillation and bleeding appeared to be less frequent in the TAVR group than in the surgery group, whereas paravalvular aortic regurgitation, valve thrombosis, and pacemaker implantation appeared to be less frequent in the surgery group.

Functional and health-status outcomes assessed according to New York Heart Association class, quality of life scores, and the percentage of patients who were alive and well at 5 years appeared to be similar in the two groups.

“These data are reassuring,” Dr. Leon said. “Cardiovascular mortality occurred at a rate of about 1% per year with both therapies, strokes at the rate of 1% per year with both therapies, and hospitalization for cardiovascular reasons at about 3% per year with both therapies. For patients in their 70s, these are very good numbers.”

Along with showing similar outcomes for TAVR and surgery at 5 years, he added, “the need for re-intervention was particularly low (2%-3%) and equivalent for both approaches. And structural valve deterioration was also very low and equivalent in both groups.”
 

Evolut low-risk trial

The Evolut trial enrolled 1,414 patients with low surgical risk who were randomly assigned to TAVR, a self-expanding supra-annular CoreValve Evolut R PRO, or surgery.

By 4 years, the primary endpoint of all-cause mortality or disabling stroke had occurred in 10.7% of the TAVR group and 14.1% in the surgery group (hazard ratio, 0.74; P = .05), representing a 26% relative reduction with TAVR.

The absolute difference between treatment arms for the primary endpoint continued to increase over time: 1.8% at 1 year, 2.0% at 2 years, 2.9% at 3 years, and 3.4% at 4 years.

Rates of the primary endpoint components were all-cause mortality 9.0% with TAVR vs. 12.1% with surgery (P = .07); and disabling stroke was 2.9% with TAVR) vs. 3.8% for surgery (P = .32). Aortic valve rehospitalization was 10.3% with TAVR vs. 12.1% with surgery (P = .27).

The composite of all-cause mortality, disabling stroke, or aortic valve rehospitalization was significantly lower with TAVR, compared with surgery (18.0% vs. 22.4%; HR, 0.78; P = .04).

New permanent pacemaker implantation was significantly higher in the TAVR group (24.6% vs. 9.9%).

Indicators of valve performance including aortic valve reintervention (1.3% TAVR vs. 1.7% surgery); clinical or subclinical valve thrombosis (0.7% TAVR vs. 0.6% surgery); and valve endocarditis (0.9% TAVR vs. 2.2% surgery) were similarly low between groups, the authors report.

TAVR patients had sustained improvement in hemodynamics as measured by echocardiography, with significantly lower aortic valve mean gradients (9.8 mm Hg TAVR vs. 12.1 mm Hg surgery) and greater effective orifice area (2.1 cm² TAVR vs. 2.0 cm² surgery).

At 4 years, 84.7% of TAVR patients and 98.4% of surgery patients had no or trace paravalvular regurgitation, and there was no difference between groups in moderate or greater paravalvular regurgitation (0.4% TAVR vs. 0.0% surgery).

“The Evolut valve has shown a superior performance to surgery,” Dr. Reardon concluded. “It has less structural valve deterioration, less severe patient prosthetic mismatch, and superior hemodynamics, compared to surgery. All these factors are translating into a widening difference in clinical event curves year on year with the Evolut valve vs. surgery.”
 

Why the difference between trials?

The big question is why the early benefit seen with TAVR vs. surgery in both trials was attenuated by 5 years in PARTNER-3 but seemed to become greater each year in the Evolut trial. There were no definite explanations for these observations, but several possibilities were suggested.

Dr. Leon noted that with trials of intervention vs. surgery, it is common for the intervention group to do better in the beginning and for surgery to catch up a bit in later years. “So, it is not that much of a surprise to see outcomes plateauing in PARTNER-3.”

But he also suggested some other factors that may have played a role, one of which was the COVID pandemic.

“During the 2-year COVID period more than 75% of the deaths and strokes in the trial occurred in the TAVR patients,” he said. “Surgery patients were getting more anticoagulation because they had more paroxysmal [atrial fibrillation]. We know that COVID is a stimulus of thrombogenic events so in an odd way we think there may have been some cardioprotective effects from anticoagulation therapy in the surgery group.”

He also pointed out that though hospitalization and strokes were slightly lower with TAVR vs. surgery in the PARTNER-3 trial, mortality was slightly greater in the TAVR group.

“There was a 2:1 ratio in the TAVR and surgery groups in noncardiovascular deaths which influenced the all-cause mortality numbers,” he noted.
 

Mortality rates in the surgery groups

Dr. Leon also pointed out differences in the mortality rates in the surgery groups in the two trials, which he suggested may contribute to the explanation for the different longer-term results.

“The baseline characteristics for patients in these two trials were almost identical, and results at 1 year were very similar, but for whatever reason, over the course of a few years, the outcomes in the Evolut trial were different to those in PARTNER-3, and in particular the difference was in the surgical arms, with a higher event rate in the surgical arm in Evolut than in the surgery arm in PARTNER-3,” he said. “When the control does not perform well it is a lot easier to show that the experimental arm is better.”

“When you look at the TAVR arms in both studies at each time point they are either similar or PARTNER-3 is actually lower,” he added. “That is why it is so difficult to compare these two trials.”

But Dr. Reardon dismissed this argument.

“What determines long-term survival after a procedure is the intrinsic risk level of the patients,” he said. “Overall mortality rates differ between the two trials because the PARTNER-3 trial enrolled a lower end of a low-risk population while Evolut enrolled an upper end of a low-risk population. You cannot look at absolute numbers between trials. That is intellectually and scientifically invalid.”

“It is the relative difference between surgery and TAVR that we are interested in, and we see in Evolut that the relative difference between the two procedures in terms of benefit with TAVR is widening every year,” he added. “That is because the superior valve performance and hemodynamics of the Evolut valve compared to surgery has translated into excellent clinical outcomes.

“In the PARTNER-3 trial – their curves are coming together. I think that is worrisome, but I don’t want to draw conclusions about their trial,” Dr. Reardon said. “All I know is that in our trial, we have excellent outcomes that are getting better year after year.”
 

Competition between valves

The different results of the two trials is inevitably producing some competition between the two products.

Dr. Reardon said: “In terms of which valve to use, clinicians will want to choose a valve that has the best durability and shows the best survival vs. surgery and that is clearly the Evolut valve. I think the writing is on the wall. Some clinicians are going to wait for longer term data, but the question is do we have enough long-term data now.”

But Dr. Leon countered: “There’s never been a head-to-head device to suggest that the self- expanding device performs better than the balloon expanding device. We always think about them as being similar in terms of performance. There is an aggressive effort to suggest that by virtue of the current trial results there was a superior outcome with the Medtronic device, but it’s hard to explain why that would be the case, and we should not compare between the two trials.”

Both Dr. Leon and Dr. Reardon stressed that longer-term follow-up is critical because some surgical valves are known to fail between 5-10 years, and it is not known how the TAVR valves will perform over that period.

Both the PARTNER-3 and Evolut trials are planning to keep following patients out to 10 years.

For the time being though, both Dr. Leon and Dr. Reardon agreed that these current results will probably accelerate the already rapid transition from surgery to TAVR in low-risk patients.

“TAVR will be the default therapy,” Dr. Leon commented. “It will be the first choice for patients. Whether TAVR is superior to surgery in terms of outcomes or just the same, there are sufficient benefits from a logistic and patient perspective that most people would prefer to have the less invasive therapy. TAVR is a one-day procedure, there is no need for general anesthetic, a lot of the secondary outcomes that are so problematic with surgery don’t exist, and the ability to be in a symptom-free state is dramatically accelerated.”

“This was the first serious foray into the low-risk population with TAVR,” he added. “We had an age cut of 65 years, but the vast majority of patients in both trials were over 70. We could now start looking at younger patient populations.”

But Dr. Reardon said that these younger patients are already being given TAVR, and future trials randomizing between TAVR and surgery may not be possible.

“Even though US guidelines still recommend surgery for patients under 65 years, patients want TAVR, and they get TAVR,” he said. “Recent data shows that in 2021, use of TAVR rose to 47.5% in patients under 65 needing isolated aortic valve replacement. That doesn’t meet the guidelines but there’s clearly a big shift going on. These results will just keep that momentum going.”

The PARTNER-3 trial was funded by Edwards Lifesciences. The Evolut study was funded by Medtronic. Dr. Leon reports grant support from Edwards Lifesciences and Medtronic. Dr. Reardon receives research grants from Medtronic.

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

The latest results from long-term follow-up of the two trials evaluating transcatheter aortic-valve replacement (TAVR) vs. surgery in patients with low surgical risk have shown different results.

The PARTNER-3 and Evolut trials were heralded as a landmark advance in medicine when the 1-year results from the two studies were presented back in 2019. Both trials suggested benefits of the less-invasive TAVR approach over surgery.

But because these low-surgical-risk patients are younger and will likely have a longer lifespan than will higher risk patients for whom the TAVR technique was first established, patient outcomes and information on how the TAVR devices hold up over the long-term are critical to inform clinical decision-making.

Latest results from the two trials show that the initial benefits of TAVR over surgery seen in PARTNER-3 seem to have attenuated over the longer-term, with main outcomes looking very similar in both groups after 5 years.

However, in the Evolut trial, the early benefit in all-cause mortality or disabling stroke seen in the TAVR group is continuing to increase, with current results showing a 26% relative reduction in this endpoint with TAVR vs. surgery at 4 years.

The 5-year results of the PARTNER-3 trial and the 4-year results of the Evolut study were presented Transcatheter Cardiovascular Therapeutics annual meeting sponsored by the Cardiovascular Research Foundation. Both sets of results were simultaneously published online: PARTNER-3 in The New England Journal of Medicine and Evolut in JACC.

Marty Leon, MD, of NewYork-Presbyterian Columbia University Irving Medical Center, who presented the PARTNER-3 results, said in an interview that both trials are good news for TAVR:

“Both trials have clearly reaffirmed clinical and echocardiographic benefits of TAVR as a meaningful alternative therapy to surgery in low-risk severe symptomatic aortic stenosis patients.” Michael Reardon, MD, Houston Methodist Debakey Heart & Vascular Center, who presented the Evolut results, agreed that both trials were positive for TAVR “as TAVR just has to be as good as surgery to be a winner because clearly it is a lot less invasive.”

But Dr. Dr. Reardon added that, “In making that decision for younger lower-risk patients, then the Evolut valve is the only TAVR valve that has shown superior hemodynamics and durability at all time points with excellent outcomes and widening benefits compared with surgery over the first 4 years.”
 

PARTNER-3

The PARTNER-3 trial randomly assigned 1,000 patients with severe symptomatic aortic stenosis and low surgical risk to undergo either TAVR with the SAPIEN 3 transcatheter heart valve or surgery.

The results at 5 years show no difference in the two primary composite outcomes between TAVR and surgery patients.

The incidence of the composite end point of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure was similar in the TAVR group and the surgery group, occurring in 22.8% of patients in the TAVR group and 27.2% in the surgery group, which is a nonsignificant difference (P = .07).

The incidence of the individual components of the composite end point were also similar in the two groups. Death occurred in 10.0% in the TAVR group and 8.2% in the surgery group; stroke in 5.8% of the TAVR group and 6.4% of the surgery group; and rehospitalization in 13.7% and 17.4%, respectively.

Aortic-valve durability also looked similar in the two groups. The hemodynamic performance of the valve, assessed according to the mean valve gradient, was 12.8 mm Hg in the TAVR group and 11.7 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group.

Among the secondary end points, atrial fibrillation and bleeding appeared to be less frequent in the TAVR group than in the surgery group, whereas paravalvular aortic regurgitation, valve thrombosis, and pacemaker implantation appeared to be less frequent in the surgery group.

Functional and health-status outcomes assessed according to New York Heart Association class, quality of life scores, and the percentage of patients who were alive and well at 5 years appeared to be similar in the two groups.

“These data are reassuring,” Dr. Leon said. “Cardiovascular mortality occurred at a rate of about 1% per year with both therapies, strokes at the rate of 1% per year with both therapies, and hospitalization for cardiovascular reasons at about 3% per year with both therapies. For patients in their 70s, these are very good numbers.”

Along with showing similar outcomes for TAVR and surgery at 5 years, he added, “the need for re-intervention was particularly low (2%-3%) and equivalent for both approaches. And structural valve deterioration was also very low and equivalent in both groups.”
 

Evolut low-risk trial

The Evolut trial enrolled 1,414 patients with low surgical risk who were randomly assigned to TAVR, a self-expanding supra-annular CoreValve Evolut R PRO, or surgery.

By 4 years, the primary endpoint of all-cause mortality or disabling stroke had occurred in 10.7% of the TAVR group and 14.1% in the surgery group (hazard ratio, 0.74; P = .05), representing a 26% relative reduction with TAVR.

The absolute difference between treatment arms for the primary endpoint continued to increase over time: 1.8% at 1 year, 2.0% at 2 years, 2.9% at 3 years, and 3.4% at 4 years.

Rates of the primary endpoint components were all-cause mortality 9.0% with TAVR vs. 12.1% with surgery (P = .07); and disabling stroke was 2.9% with TAVR) vs. 3.8% for surgery (P = .32). Aortic valve rehospitalization was 10.3% with TAVR vs. 12.1% with surgery (P = .27).

The composite of all-cause mortality, disabling stroke, or aortic valve rehospitalization was significantly lower with TAVR, compared with surgery (18.0% vs. 22.4%; HR, 0.78; P = .04).

New permanent pacemaker implantation was significantly higher in the TAVR group (24.6% vs. 9.9%).

Indicators of valve performance including aortic valve reintervention (1.3% TAVR vs. 1.7% surgery); clinical or subclinical valve thrombosis (0.7% TAVR vs. 0.6% surgery); and valve endocarditis (0.9% TAVR vs. 2.2% surgery) were similarly low between groups, the authors report.

TAVR patients had sustained improvement in hemodynamics as measured by echocardiography, with significantly lower aortic valve mean gradients (9.8 mm Hg TAVR vs. 12.1 mm Hg surgery) and greater effective orifice area (2.1 cm² TAVR vs. 2.0 cm² surgery).

At 4 years, 84.7% of TAVR patients and 98.4% of surgery patients had no or trace paravalvular regurgitation, and there was no difference between groups in moderate or greater paravalvular regurgitation (0.4% TAVR vs. 0.0% surgery).

“The Evolut valve has shown a superior performance to surgery,” Dr. Reardon concluded. “It has less structural valve deterioration, less severe patient prosthetic mismatch, and superior hemodynamics, compared to surgery. All these factors are translating into a widening difference in clinical event curves year on year with the Evolut valve vs. surgery.”
 

Why the difference between trials?

The big question is why the early benefit seen with TAVR vs. surgery in both trials was attenuated by 5 years in PARTNER-3 but seemed to become greater each year in the Evolut trial. There were no definite explanations for these observations, but several possibilities were suggested.

Dr. Leon noted that with trials of intervention vs. surgery, it is common for the intervention group to do better in the beginning and for surgery to catch up a bit in later years. “So, it is not that much of a surprise to see outcomes plateauing in PARTNER-3.”

But he also suggested some other factors that may have played a role, one of which was the COVID pandemic.

“During the 2-year COVID period more than 75% of the deaths and strokes in the trial occurred in the TAVR patients,” he said. “Surgery patients were getting more anticoagulation because they had more paroxysmal [atrial fibrillation]. We know that COVID is a stimulus of thrombogenic events so in an odd way we think there may have been some cardioprotective effects from anticoagulation therapy in the surgery group.”

He also pointed out that though hospitalization and strokes were slightly lower with TAVR vs. surgery in the PARTNER-3 trial, mortality was slightly greater in the TAVR group.

“There was a 2:1 ratio in the TAVR and surgery groups in noncardiovascular deaths which influenced the all-cause mortality numbers,” he noted.
 

Mortality rates in the surgery groups

Dr. Leon also pointed out differences in the mortality rates in the surgery groups in the two trials, which he suggested may contribute to the explanation for the different longer-term results.

“The baseline characteristics for patients in these two trials were almost identical, and results at 1 year were very similar, but for whatever reason, over the course of a few years, the outcomes in the Evolut trial were different to those in PARTNER-3, and in particular the difference was in the surgical arms, with a higher event rate in the surgical arm in Evolut than in the surgery arm in PARTNER-3,” he said. “When the control does not perform well it is a lot easier to show that the experimental arm is better.”

“When you look at the TAVR arms in both studies at each time point they are either similar or PARTNER-3 is actually lower,” he added. “That is why it is so difficult to compare these two trials.”

But Dr. Reardon dismissed this argument.

“What determines long-term survival after a procedure is the intrinsic risk level of the patients,” he said. “Overall mortality rates differ between the two trials because the PARTNER-3 trial enrolled a lower end of a low-risk population while Evolut enrolled an upper end of a low-risk population. You cannot look at absolute numbers between trials. That is intellectually and scientifically invalid.”

“It is the relative difference between surgery and TAVR that we are interested in, and we see in Evolut that the relative difference between the two procedures in terms of benefit with TAVR is widening every year,” he added. “That is because the superior valve performance and hemodynamics of the Evolut valve compared to surgery has translated into excellent clinical outcomes.

“In the PARTNER-3 trial – their curves are coming together. I think that is worrisome, but I don’t want to draw conclusions about their trial,” Dr. Reardon said. “All I know is that in our trial, we have excellent outcomes that are getting better year after year.”
 

Competition between valves

The different results of the two trials is inevitably producing some competition between the two products.

Dr. Reardon said: “In terms of which valve to use, clinicians will want to choose a valve that has the best durability and shows the best survival vs. surgery and that is clearly the Evolut valve. I think the writing is on the wall. Some clinicians are going to wait for longer term data, but the question is do we have enough long-term data now.”

But Dr. Leon countered: “There’s never been a head-to-head device to suggest that the self- expanding device performs better than the balloon expanding device. We always think about them as being similar in terms of performance. There is an aggressive effort to suggest that by virtue of the current trial results there was a superior outcome with the Medtronic device, but it’s hard to explain why that would be the case, and we should not compare between the two trials.”

Both Dr. Leon and Dr. Reardon stressed that longer-term follow-up is critical because some surgical valves are known to fail between 5-10 years, and it is not known how the TAVR valves will perform over that period.

Both the PARTNER-3 and Evolut trials are planning to keep following patients out to 10 years.

For the time being though, both Dr. Leon and Dr. Reardon agreed that these current results will probably accelerate the already rapid transition from surgery to TAVR in low-risk patients.

“TAVR will be the default therapy,” Dr. Leon commented. “It will be the first choice for patients. Whether TAVR is superior to surgery in terms of outcomes or just the same, there are sufficient benefits from a logistic and patient perspective that most people would prefer to have the less invasive therapy. TAVR is a one-day procedure, there is no need for general anesthetic, a lot of the secondary outcomes that are so problematic with surgery don’t exist, and the ability to be in a symptom-free state is dramatically accelerated.”

“This was the first serious foray into the low-risk population with TAVR,” he added. “We had an age cut of 65 years, but the vast majority of patients in both trials were over 70. We could now start looking at younger patient populations.”

But Dr. Reardon said that these younger patients are already being given TAVR, and future trials randomizing between TAVR and surgery may not be possible.

“Even though US guidelines still recommend surgery for patients under 65 years, patients want TAVR, and they get TAVR,” he said. “Recent data shows that in 2021, use of TAVR rose to 47.5% in patients under 65 needing isolated aortic valve replacement. That doesn’t meet the guidelines but there’s clearly a big shift going on. These results will just keep that momentum going.”

The PARTNER-3 trial was funded by Edwards Lifesciences. The Evolut study was funded by Medtronic. Dr. Leon reports grant support from Edwards Lifesciences and Medtronic. Dr. Reardon receives research grants from Medtronic.

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

SAN FRANCISCO – Among patients with symptomatic, severe native aortic regurgitation at high surgical risk, the JenaValve Trilogy transcatheter heart valve system (JenaValve Technology) met its primary safety and efficacy endpoints, achieving a 1-year all-cause mortality rate of 7.8%.

New pacemaker implantation was 24%, similar to previously reported outcomes.

Vinod Thourani, MD, Piedmont Heart Institute, Atlanta, presented initial outcome results of the ALIGN-AR trial at the Transcatheter Cardiovascular Therapeutics annual meeting.

Dr. Thourani concluded that the Trilogy system provides the first dedicated transcatheter aortic valve replacement options “for symptomatic patients with moderate to severe or severe aortic regurgitation or at high risk for surgery and is well positioned to become the preferred therapy upon approval for this population.”

Currently, Trilogy is not approved by the U.S. Food and Drug Administration in the United States and is for investigational use only.

Untreated, severe symptomatic aortic regurgitation (AR) is associated with high mortality, especially for those with NYHA class 3 or 4 symptoms, Dr. Thourani explained. “While surgery remains the only recommended intervention for patients with native severe AR, there are a multitude of high-risk patients who are not offered therapy.”

Off-label use of transcatheter valves for AR has been associated with “higher rates of complications, including paravalvular regurgitation and embolization,” he noted.

Dr. Thourani described the unique features of the JenaValve Trilogy valve. The system has a set of three “locators” in its own sheath that allows it to be rotated to align with the three cusps of the native aortic valve, falling into the sinuses and securely anchored to the native valve leaflets – then the valve is deployed. Inside a self-expanding nitinol frame is porcine pericardial tissue. A sealing ring provides sufficient anchoring while conforming to the annulus.

ALIGN-AR was a multicenter, single arm, non-blinded trial with follow-up out to 5 years involving patients with 3-plus or greater AR at high risk for surgical aortic valve replacement. Exclusion criteria included an aortic root diameter greater than 5 cm, a previous prosthetic aortic valve, mitral regurgitation greater than moderate, or coronary artery disease requiring revascularization.

After Trilogy valve implantation, patients were followed for 1, 6, and 12 months, as well as annually out to 5 years. Safety and efficacy endpoints were compared with prespecified performance goals. Of 180 patients enrolled, 177 were successfully implanted with the Trilogy device.

Patients had an average age of 75.5 years, 47.2% were women, 67.2% were in NYHA class III/IV, 82.8% were hypertensive, and one-third were frail. Severe AR was present in 62.4%, and 31.7% had moderate to severe AR.

The primary composite safety endpoint included all-cause mortality, any stroke, major vascular complication, major bleeding, a new pacemaker, acute kidney injury, valve dysfunction, or any intervention related to the device. The primary efficacy endpoint was all-cause mortality at 12 months.

The performance goal for primary efficacy was a weighted average of 25%, derived mainly from 1-year mortality figures for NYHA class I/II and class II/IV with conservative management.
 

Non-inferiority margin met

With a 25% prespecified non-inferiority margin for the primary efficacy endpoint, “We have observed a rate of 7.8%,” Dr. Thourani reported during a late-breaking clinical trials session. “The non-inferiority margin was met for the primary efficacy endpoint with a P value of less than .0001.”

“With a 40.5% prespecified non-inferiority margin of our primary safety endpoint, with a Trilogy [heart valve] we have observed a rate of 26.7%,” he said. “At 30 days there was a 2.2% mortality and a 2.2% stroke rate. There was a 26.7% primary safety endpoint, mainly driven by the 24% new pacemaker implantation rate. Without pacemaker implantation, the rate of safety events was less than 8%,” (P noninferiority < .0001).

Procedure technical success was 95%, device success 96.7%, and procedure success 92.8%. There was one ascending aortic dissection (0.6%). Moderate or greater paravalvular regurgitation also occurred in one patient. There were four cases of valve embolization.

Pacemaker implants occurred in 30% of patients in the first tercile enrolled and decreased to 14% for the third tercile enrolled. “Lower rates are most likely due to the change in the insertion technique, placing locators above the nadir of the native cusps, reduction in oversizing, and also evolution in the management of periprocedural conduction abnormalities,” Dr. Thourani proposed.

The hemodynamics of the valve improved from a gradient of 8.7 mm Hg at baseline to 3.9 mm Hg at 30 days and remained fairly stable out to 1 year. Paravalvular regurgitation was absent in 80.8% of patients at 30 days and mild in 18%. It improved over time, being absent in 93.5% at 6 months and in 92.2% at 1 year.

Left ventricular (LV) remodeling occurred over one year, with LV end systolic diameter, LV end systolic volume, LV mass, and LV mass index all decreasing significantly from baseline to one year (all P < .0001). Importantly to patients, NYHA class improved, from 32% class II, 63% class III, and 5% class IV at baseline to 54% class I, 37% class II, and 10% class III at 30 days and improving slightly out to 1 year.

These improvements resulted in better quality of life, as reflected in a 21.8-point improvement in the self-reported Kansas City Cardiomyopathy Questionnaire Overall Summary Score, with a score of 77.6 at 1 year, indicating self-perceived good health.
 

Encouraging data

During the session, Robert Bonow, MD, of Northwestern University Feinberg School of Medicine, Chicago, commented that Dr. Thourani presented very encouraging data from the ALIGN-AR trial of high-risk surgical patients with significant aortic regurgitation. However, he had a couple of questions for Dr. Thourani.

One related to the efficacy data being compared with historical survival data. “So, are you planning to do a randomized study of these patients? You could argue, unlike aortic stenosis, where there’s no medical therapy, there could be medical therapies for the patients.” He noted that one-third of the patients are only in NYHA functional class II, so those patients “might do well over the long haul, with medical therapy as an agent.”

Dr. Thourani said it was an excellent question. “Doing a randomized trial with a high-risk patient [is] probably less likely,” he said. “I think there is a lot of interest among physicians on the cardiology side and on the surgery side of looking at lower-risk patients, and this could include those that are intermediate and or low risk.”

He said he believes investigators and leadership of the ALIGN-AR trial have conceived of such a trial involving all comers. “I think that’s warranted if we go into younger patients,” he said.

Dr. Bonow then asked if there was significant aortic valve calcification in the study population, because it is common with regurgitation, “which is why standard approaches are not effective ... And how does this device behave in calcified valves?” But Dr. Thourani said calcification was an exclusion criterion for this trial.

He said, “deep dives are going to come,” looking at the ventricular outcomes and also looking at a lot of the echocardiographic parameters.

Dr. Bonow related this study’s findings on ventricular remodeling to what is seen with surgical aortic valve replacement, where the ventricle decompresses within days. “And that’s predictive of good outcome if you have early data and these patients show how the ventricle remodels quickly,” he said.

The trial was supported by JenaValve. Dr. Thourani has received grant/research support from Abbott Vascular, Artivion, Atricure, Boston Scientific, CroiValve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, Atricure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Dr. Bonow had no disclosures.

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

SAN FRANCISCO – Among patients with symptomatic, severe native aortic regurgitation at high surgical risk, the JenaValve Trilogy transcatheter heart valve system (JenaValve Technology) met its primary safety and efficacy endpoints, achieving a 1-year all-cause mortality rate of 7.8%.

New pacemaker implantation was 24%, similar to previously reported outcomes.

Vinod Thourani, MD, Piedmont Heart Institute, Atlanta, presented initial outcome results of the ALIGN-AR trial at the Transcatheter Cardiovascular Therapeutics annual meeting.

Dr. Thourani concluded that the Trilogy system provides the first dedicated transcatheter aortic valve replacement options “for symptomatic patients with moderate to severe or severe aortic regurgitation or at high risk for surgery and is well positioned to become the preferred therapy upon approval for this population.”

Currently, Trilogy is not approved by the U.S. Food and Drug Administration in the United States and is for investigational use only.

Untreated, severe symptomatic aortic regurgitation (AR) is associated with high mortality, especially for those with NYHA class 3 or 4 symptoms, Dr. Thourani explained. “While surgery remains the only recommended intervention for patients with native severe AR, there are a multitude of high-risk patients who are not offered therapy.”

Off-label use of transcatheter valves for AR has been associated with “higher rates of complications, including paravalvular regurgitation and embolization,” he noted.

Dr. Thourani described the unique features of the JenaValve Trilogy valve. The system has a set of three “locators” in its own sheath that allows it to be rotated to align with the three cusps of the native aortic valve, falling into the sinuses and securely anchored to the native valve leaflets – then the valve is deployed. Inside a self-expanding nitinol frame is porcine pericardial tissue. A sealing ring provides sufficient anchoring while conforming to the annulus.

ALIGN-AR was a multicenter, single arm, non-blinded trial with follow-up out to 5 years involving patients with 3-plus or greater AR at high risk for surgical aortic valve replacement. Exclusion criteria included an aortic root diameter greater than 5 cm, a previous prosthetic aortic valve, mitral regurgitation greater than moderate, or coronary artery disease requiring revascularization.

After Trilogy valve implantation, patients were followed for 1, 6, and 12 months, as well as annually out to 5 years. Safety and efficacy endpoints were compared with prespecified performance goals. Of 180 patients enrolled, 177 were successfully implanted with the Trilogy device.

Patients had an average age of 75.5 years, 47.2% were women, 67.2% were in NYHA class III/IV, 82.8% were hypertensive, and one-third were frail. Severe AR was present in 62.4%, and 31.7% had moderate to severe AR.

The primary composite safety endpoint included all-cause mortality, any stroke, major vascular complication, major bleeding, a new pacemaker, acute kidney injury, valve dysfunction, or any intervention related to the device. The primary efficacy endpoint was all-cause mortality at 12 months.

The performance goal for primary efficacy was a weighted average of 25%, derived mainly from 1-year mortality figures for NYHA class I/II and class II/IV with conservative management.
 

Non-inferiority margin met

With a 25% prespecified non-inferiority margin for the primary efficacy endpoint, “We have observed a rate of 7.8%,” Dr. Thourani reported during a late-breaking clinical trials session. “The non-inferiority margin was met for the primary efficacy endpoint with a P value of less than .0001.”

“With a 40.5% prespecified non-inferiority margin of our primary safety endpoint, with a Trilogy [heart valve] we have observed a rate of 26.7%,” he said. “At 30 days there was a 2.2% mortality and a 2.2% stroke rate. There was a 26.7% primary safety endpoint, mainly driven by the 24% new pacemaker implantation rate. Without pacemaker implantation, the rate of safety events was less than 8%,” (P noninferiority < .0001).

Procedure technical success was 95%, device success 96.7%, and procedure success 92.8%. There was one ascending aortic dissection (0.6%). Moderate or greater paravalvular regurgitation also occurred in one patient. There were four cases of valve embolization.

Pacemaker implants occurred in 30% of patients in the first tercile enrolled and decreased to 14% for the third tercile enrolled. “Lower rates are most likely due to the change in the insertion technique, placing locators above the nadir of the native cusps, reduction in oversizing, and also evolution in the management of periprocedural conduction abnormalities,” Dr. Thourani proposed.

The hemodynamics of the valve improved from a gradient of 8.7 mm Hg at baseline to 3.9 mm Hg at 30 days and remained fairly stable out to 1 year. Paravalvular regurgitation was absent in 80.8% of patients at 30 days and mild in 18%. It improved over time, being absent in 93.5% at 6 months and in 92.2% at 1 year.

Left ventricular (LV) remodeling occurred over one year, with LV end systolic diameter, LV end systolic volume, LV mass, and LV mass index all decreasing significantly from baseline to one year (all P < .0001). Importantly to patients, NYHA class improved, from 32% class II, 63% class III, and 5% class IV at baseline to 54% class I, 37% class II, and 10% class III at 30 days and improving slightly out to 1 year.

These improvements resulted in better quality of life, as reflected in a 21.8-point improvement in the self-reported Kansas City Cardiomyopathy Questionnaire Overall Summary Score, with a score of 77.6 at 1 year, indicating self-perceived good health.
 

Encouraging data

During the session, Robert Bonow, MD, of Northwestern University Feinberg School of Medicine, Chicago, commented that Dr. Thourani presented very encouraging data from the ALIGN-AR trial of high-risk surgical patients with significant aortic regurgitation. However, he had a couple of questions for Dr. Thourani.

One related to the efficacy data being compared with historical survival data. “So, are you planning to do a randomized study of these patients? You could argue, unlike aortic stenosis, where there’s no medical therapy, there could be medical therapies for the patients.” He noted that one-third of the patients are only in NYHA functional class II, so those patients “might do well over the long haul, with medical therapy as an agent.”

Dr. Thourani said it was an excellent question. “Doing a randomized trial with a high-risk patient [is] probably less likely,” he said. “I think there is a lot of interest among physicians on the cardiology side and on the surgery side of looking at lower-risk patients, and this could include those that are intermediate and or low risk.”

He said he believes investigators and leadership of the ALIGN-AR trial have conceived of such a trial involving all comers. “I think that’s warranted if we go into younger patients,” he said.

Dr. Bonow then asked if there was significant aortic valve calcification in the study population, because it is common with regurgitation, “which is why standard approaches are not effective ... And how does this device behave in calcified valves?” But Dr. Thourani said calcification was an exclusion criterion for this trial.

He said, “deep dives are going to come,” looking at the ventricular outcomes and also looking at a lot of the echocardiographic parameters.

Dr. Bonow related this study’s findings on ventricular remodeling to what is seen with surgical aortic valve replacement, where the ventricle decompresses within days. “And that’s predictive of good outcome if you have early data and these patients show how the ventricle remodels quickly,” he said.

The trial was supported by JenaValve. Dr. Thourani has received grant/research support from Abbott Vascular, Artivion, Atricure, Boston Scientific, CroiValve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, Atricure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Dr. Bonow had no disclosures.

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

SAN FRANCISCO – Among patients with symptomatic, severe native aortic regurgitation at high surgical risk, the JenaValve Trilogy transcatheter heart valve system (JenaValve Technology) met its primary safety and efficacy endpoints, achieving a 1-year all-cause mortality rate of 7.8%.

New pacemaker implantation was 24%, similar to previously reported outcomes.

Vinod Thourani, MD, Piedmont Heart Institute, Atlanta, presented initial outcome results of the ALIGN-AR trial at the Transcatheter Cardiovascular Therapeutics annual meeting.

Dr. Thourani concluded that the Trilogy system provides the first dedicated transcatheter aortic valve replacement options “for symptomatic patients with moderate to severe or severe aortic regurgitation or at high risk for surgery and is well positioned to become the preferred therapy upon approval for this population.”

Currently, Trilogy is not approved by the U.S. Food and Drug Administration in the United States and is for investigational use only.

Untreated, severe symptomatic aortic regurgitation (AR) is associated with high mortality, especially for those with NYHA class 3 or 4 symptoms, Dr. Thourani explained. “While surgery remains the only recommended intervention for patients with native severe AR, there are a multitude of high-risk patients who are not offered therapy.”

Off-label use of transcatheter valves for AR has been associated with “higher rates of complications, including paravalvular regurgitation and embolization,” he noted.

Dr. Thourani described the unique features of the JenaValve Trilogy valve. The system has a set of three “locators” in its own sheath that allows it to be rotated to align with the three cusps of the native aortic valve, falling into the sinuses and securely anchored to the native valve leaflets – then the valve is deployed. Inside a self-expanding nitinol frame is porcine pericardial tissue. A sealing ring provides sufficient anchoring while conforming to the annulus.

ALIGN-AR was a multicenter, single arm, non-blinded trial with follow-up out to 5 years involving patients with 3-plus or greater AR at high risk for surgical aortic valve replacement. Exclusion criteria included an aortic root diameter greater than 5 cm, a previous prosthetic aortic valve, mitral regurgitation greater than moderate, or coronary artery disease requiring revascularization.

After Trilogy valve implantation, patients were followed for 1, 6, and 12 months, as well as annually out to 5 years. Safety and efficacy endpoints were compared with prespecified performance goals. Of 180 patients enrolled, 177 were successfully implanted with the Trilogy device.

Patients had an average age of 75.5 years, 47.2% were women, 67.2% were in NYHA class III/IV, 82.8% were hypertensive, and one-third were frail. Severe AR was present in 62.4%, and 31.7% had moderate to severe AR.

The primary composite safety endpoint included all-cause mortality, any stroke, major vascular complication, major bleeding, a new pacemaker, acute kidney injury, valve dysfunction, or any intervention related to the device. The primary efficacy endpoint was all-cause mortality at 12 months.

The performance goal for primary efficacy was a weighted average of 25%, derived mainly from 1-year mortality figures for NYHA class I/II and class II/IV with conservative management.
 

Non-inferiority margin met

With a 25% prespecified non-inferiority margin for the primary efficacy endpoint, “We have observed a rate of 7.8%,” Dr. Thourani reported during a late-breaking clinical trials session. “The non-inferiority margin was met for the primary efficacy endpoint with a P value of less than .0001.”

“With a 40.5% prespecified non-inferiority margin of our primary safety endpoint, with a Trilogy [heart valve] we have observed a rate of 26.7%,” he said. “At 30 days there was a 2.2% mortality and a 2.2% stroke rate. There was a 26.7% primary safety endpoint, mainly driven by the 24% new pacemaker implantation rate. Without pacemaker implantation, the rate of safety events was less than 8%,” (P noninferiority < .0001).

Procedure technical success was 95%, device success 96.7%, and procedure success 92.8%. There was one ascending aortic dissection (0.6%). Moderate or greater paravalvular regurgitation also occurred in one patient. There were four cases of valve embolization.

Pacemaker implants occurred in 30% of patients in the first tercile enrolled and decreased to 14% for the third tercile enrolled. “Lower rates are most likely due to the change in the insertion technique, placing locators above the nadir of the native cusps, reduction in oversizing, and also evolution in the management of periprocedural conduction abnormalities,” Dr. Thourani proposed.

The hemodynamics of the valve improved from a gradient of 8.7 mm Hg at baseline to 3.9 mm Hg at 30 days and remained fairly stable out to 1 year. Paravalvular regurgitation was absent in 80.8% of patients at 30 days and mild in 18%. It improved over time, being absent in 93.5% at 6 months and in 92.2% at 1 year.

Left ventricular (LV) remodeling occurred over one year, with LV end systolic diameter, LV end systolic volume, LV mass, and LV mass index all decreasing significantly from baseline to one year (all P < .0001). Importantly to patients, NYHA class improved, from 32% class II, 63% class III, and 5% class IV at baseline to 54% class I, 37% class II, and 10% class III at 30 days and improving slightly out to 1 year.

These improvements resulted in better quality of life, as reflected in a 21.8-point improvement in the self-reported Kansas City Cardiomyopathy Questionnaire Overall Summary Score, with a score of 77.6 at 1 year, indicating self-perceived good health.
 

Encouraging data

During the session, Robert Bonow, MD, of Northwestern University Feinberg School of Medicine, Chicago, commented that Dr. Thourani presented very encouraging data from the ALIGN-AR trial of high-risk surgical patients with significant aortic regurgitation. However, he had a couple of questions for Dr. Thourani.

One related to the efficacy data being compared with historical survival data. “So, are you planning to do a randomized study of these patients? You could argue, unlike aortic stenosis, where there’s no medical therapy, there could be medical therapies for the patients.” He noted that one-third of the patients are only in NYHA functional class II, so those patients “might do well over the long haul, with medical therapy as an agent.”

Dr. Thourani said it was an excellent question. “Doing a randomized trial with a high-risk patient [is] probably less likely,” he said. “I think there is a lot of interest among physicians on the cardiology side and on the surgery side of looking at lower-risk patients, and this could include those that are intermediate and or low risk.”

He said he believes investigators and leadership of the ALIGN-AR trial have conceived of such a trial involving all comers. “I think that’s warranted if we go into younger patients,” he said.

Dr. Bonow then asked if there was significant aortic valve calcification in the study population, because it is common with regurgitation, “which is why standard approaches are not effective ... And how does this device behave in calcified valves?” But Dr. Thourani said calcification was an exclusion criterion for this trial.

He said, “deep dives are going to come,” looking at the ventricular outcomes and also looking at a lot of the echocardiographic parameters.

Dr. Bonow related this study’s findings on ventricular remodeling to what is seen with surgical aortic valve replacement, where the ventricle decompresses within days. “And that’s predictive of good outcome if you have early data and these patients show how the ventricle remodels quickly,” he said.

The trial was supported by JenaValve. Dr. Thourani has received grant/research support from Abbott Vascular, Artivion, Atricure, Boston Scientific, CroiValve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, Atricure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Dr. Bonow had no disclosures.

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

Commercial sperm banks in the United States lack racially and ethnically diverse donors, potentially limiting family-planning options for patients in traditionally underserved populations, according to a study presented at the American Society for Reproductive Medicine’s 2023 meeting.

“This really highlights the need to identify barriers to increase recruitment of these donors so that we can support family-building for all populations,” said Lauren Gibbs, MD, a resident in the department of obstetrics and gynecology at the Morehouse School of Medicine in Atlanta.

Dr. Gibbs and her colleagues compared the racial and ethnic makeup of sperm donors from online and self-reported profiles at 14 of the largest donor banks in the United States for March and April of 2023. Historical data were pulled from two large, national banks. The investigators compared these data to census estimates from 2021 for men between the ages of 18 and 44 years.

Donors who identified as Hispanic (10.9%) or Black (3.3%) were significantly underrepresented as compared to the U.S. population, of which Hispanic men compose 22% and Black men make up 13.3%.

Asian donors were overrepresented, making up 21.9% of the donors but only 6.5% of the U.S. population. White donors were proportionately represented in relation to national demographics, making up 56.6% of the donors and representing 55% of the U.S. population, according to the researchers. None of the donors identified as Native/Hawaiian/Pacific Islander or American Indian/Alaskan Natives; these groups represent 0.22% and 0.79% of the U.S. population, respectively.

“Next steps will be figuring out why this is happening and how to address it,” said Valerie L Baker, MD, director in the division of reproductive endocrinology and infertility at Johns Hopkins Medicine in Lutherville, Md., who was not involved in the study.

The study sheds light on the need to identify and address the barriers that discourage potential donors from underrepresented groups from participating in sperm donation, according to Kimball Pomeroy, PhD, scientific director at the World Egg and Sperm Bank in Scottsdale, Ariz.

“Sometimes there are inhibitors of different ethnic groups to want to act as sperm or egg donors, so trying to understand if that’s the case is important; but I’m sure a lot of it is also related to access,” Dr. Pomeroy, who was not part of the study team, said in an interview.

Longitudinal data from the two national donor banks did not indicate any significant increase or decrease in donation trends across the 5-year period from 2018 to 2022, highlighting the persisting issue of representation disparities. Dr. Gibbs said strategies need to be developed to increase recruitment of donors from underrepresented groups. Increasing the diversity of the donor pool will ultimately support family-building options for all patients, according to Dr. Gibbs.

Funding for the study was provided by the EMD Serono REI Diversity Fellowship Grant. Dr. Gibbs reports no relevant financial relationships.

Commercial sperm banks in the United States lack racially and ethnically diverse donors, potentially limiting family-planning options for patients in traditionally underserved populations, according to a study presented at the American Society for Reproductive Medicine’s 2023 meeting.

“This really highlights the need to identify barriers to increase recruitment of these donors so that we can support family-building for all populations,” said Lauren Gibbs, MD, a resident in the department of obstetrics and gynecology at the Morehouse School of Medicine in Atlanta.

Dr. Gibbs and her colleagues compared the racial and ethnic makeup of sperm donors from online and self-reported profiles at 14 of the largest donor banks in the United States for March and April of 2023. Historical data were pulled from two large, national banks. The investigators compared these data to census estimates from 2021 for men between the ages of 18 and 44 years.

Donors who identified as Hispanic (10.9%) or Black (3.3%) were significantly underrepresented as compared to the U.S. population, of which Hispanic men compose 22% and Black men make up 13.3%.

Asian donors were overrepresented, making up 21.9% of the donors but only 6.5% of the U.S. population. White donors were proportionately represented in relation to national demographics, making up 56.6% of the donors and representing 55% of the U.S. population, according to the researchers. None of the donors identified as Native/Hawaiian/Pacific Islander or American Indian/Alaskan Natives; these groups represent 0.22% and 0.79% of the U.S. population, respectively.

“Next steps will be figuring out why this is happening and how to address it,” said Valerie L Baker, MD, director in the division of reproductive endocrinology and infertility at Johns Hopkins Medicine in Lutherville, Md., who was not involved in the study.

The study sheds light on the need to identify and address the barriers that discourage potential donors from underrepresented groups from participating in sperm donation, according to Kimball Pomeroy, PhD, scientific director at the World Egg and Sperm Bank in Scottsdale, Ariz.

“Sometimes there are inhibitors of different ethnic groups to want to act as sperm or egg donors, so trying to understand if that’s the case is important; but I’m sure a lot of it is also related to access,” Dr. Pomeroy, who was not part of the study team, said in an interview.

Longitudinal data from the two national donor banks did not indicate any significant increase or decrease in donation trends across the 5-year period from 2018 to 2022, highlighting the persisting issue of representation disparities. Dr. Gibbs said strategies need to be developed to increase recruitment of donors from underrepresented groups. Increasing the diversity of the donor pool will ultimately support family-building options for all patients, according to Dr. Gibbs.

Funding for the study was provided by the EMD Serono REI Diversity Fellowship Grant. Dr. Gibbs reports no relevant financial relationships.

Commercial sperm banks in the United States lack racially and ethnically diverse donors, potentially limiting family-planning options for patients in traditionally underserved populations, according to a study presented at the American Society for Reproductive Medicine’s 2023 meeting.

“This really highlights the need to identify barriers to increase recruitment of these donors so that we can support family-building for all populations,” said Lauren Gibbs, MD, a resident in the department of obstetrics and gynecology at the Morehouse School of Medicine in Atlanta.

Dr. Gibbs and her colleagues compared the racial and ethnic makeup of sperm donors from online and self-reported profiles at 14 of the largest donor banks in the United States for March and April of 2023. Historical data were pulled from two large, national banks. The investigators compared these data to census estimates from 2021 for men between the ages of 18 and 44 years.

Donors who identified as Hispanic (10.9%) or Black (3.3%) were significantly underrepresented as compared to the U.S. population, of which Hispanic men compose 22% and Black men make up 13.3%.

Asian donors were overrepresented, making up 21.9% of the donors but only 6.5% of the U.S. population. White donors were proportionately represented in relation to national demographics, making up 56.6% of the donors and representing 55% of the U.S. population, according to the researchers. None of the donors identified as Native/Hawaiian/Pacific Islander or American Indian/Alaskan Natives; these groups represent 0.22% and 0.79% of the U.S. population, respectively.

“Next steps will be figuring out why this is happening and how to address it,” said Valerie L Baker, MD, director in the division of reproductive endocrinology and infertility at Johns Hopkins Medicine in Lutherville, Md., who was not involved in the study.

The study sheds light on the need to identify and address the barriers that discourage potential donors from underrepresented groups from participating in sperm donation, according to Kimball Pomeroy, PhD, scientific director at the World Egg and Sperm Bank in Scottsdale, Ariz.

“Sometimes there are inhibitors of different ethnic groups to want to act as sperm or egg donors, so trying to understand if that’s the case is important; but I’m sure a lot of it is also related to access,” Dr. Pomeroy, who was not part of the study team, said in an interview.

Longitudinal data from the two national donor banks did not indicate any significant increase or decrease in donation trends across the 5-year period from 2018 to 2022, highlighting the persisting issue of representation disparities. Dr. Gibbs said strategies need to be developed to increase recruitment of donors from underrepresented groups. Increasing the diversity of the donor pool will ultimately support family-building options for all patients, according to Dr. Gibbs.

Funding for the study was provided by the EMD Serono REI Diversity Fellowship Grant. Dr. Gibbs reports no relevant financial relationships.

Access to technology, particularly cellphones, is tied to a higher awareness of pre-exposure prophylaxis (PrEP) in women, according to survey results presented at the Association of Nurses in AIDS Care 2023 Annual Meeting.

Those with limited access to technology, older women, and women who had been incarcerated were also less likely to be aware of their medication options.

Researchers collected responses from 206 women in New York and Philadelphia by computer survey. The women were HIV negative and eligible to receive medication but were not currently taking any.

Most participants were Black (61%) or Hispanic (24%), and the average age of participants was 39 years. Nearly 60% of the group reported they were not aware of PrEP.

Younger women, Hispanic women, women who had not been incarcerated, and women with access to technology were most likely to be aware that they could take medication to prevent HIV.

“Women who utilized their cell phones for activities such as texting, emailing, watching videos, playing games, downloading apps, and accessing social media were more likely to be aware of PrEP,” point out the researchers led by Su Kyung Kim, PhD, WHNP-BC, an assistant professor at Thomas Jefferson University, Philadelphia.

These findings could help direct efforts to increase awareness among women where uptake has remained low, the researchers report. “Mobile technologies, in particular, offer a nimble, customizable, and accessible way to reach this target population and increase awareness of PrEP.”

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

Access to technology, particularly cellphones, is tied to a higher awareness of pre-exposure prophylaxis (PrEP) in women, according to survey results presented at the Association of Nurses in AIDS Care 2023 Annual Meeting.

Those with limited access to technology, older women, and women who had been incarcerated were also less likely to be aware of their medication options.

Researchers collected responses from 206 women in New York and Philadelphia by computer survey. The women were HIV negative and eligible to receive medication but were not currently taking any.

Most participants were Black (61%) or Hispanic (24%), and the average age of participants was 39 years. Nearly 60% of the group reported they were not aware of PrEP.

Younger women, Hispanic women, women who had not been incarcerated, and women with access to technology were most likely to be aware that they could take medication to prevent HIV.

“Women who utilized their cell phones for activities such as texting, emailing, watching videos, playing games, downloading apps, and accessing social media were more likely to be aware of PrEP,” point out the researchers led by Su Kyung Kim, PhD, WHNP-BC, an assistant professor at Thomas Jefferson University, Philadelphia.

These findings could help direct efforts to increase awareness among women where uptake has remained low, the researchers report. “Mobile technologies, in particular, offer a nimble, customizable, and accessible way to reach this target population and increase awareness of PrEP.”

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

Access to technology, particularly cellphones, is tied to a higher awareness of pre-exposure prophylaxis (PrEP) in women, according to survey results presented at the Association of Nurses in AIDS Care 2023 Annual Meeting.

Those with limited access to technology, older women, and women who had been incarcerated were also less likely to be aware of their medication options.

Researchers collected responses from 206 women in New York and Philadelphia by computer survey. The women were HIV negative and eligible to receive medication but were not currently taking any.

Most participants were Black (61%) or Hispanic (24%), and the average age of participants was 39 years. Nearly 60% of the group reported they were not aware of PrEP.

Younger women, Hispanic women, women who had not been incarcerated, and women with access to technology were most likely to be aware that they could take medication to prevent HIV.

“Women who utilized their cell phones for activities such as texting, emailing, watching videos, playing games, downloading apps, and accessing social media were more likely to be aware of PrEP,” point out the researchers led by Su Kyung Kim, PhD, WHNP-BC, an assistant professor at Thomas Jefferson University, Philadelphia.

These findings could help direct efforts to increase awareness among women where uptake has remained low, the researchers report. “Mobile technologies, in particular, offer a nimble, customizable, and accessible way to reach this target population and increase awareness of PrEP.”

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.

Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.

“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.

Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.

Dr. Strunc offered a few more tips for diagnosing a child:

• Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
• Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
• Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
• Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.

The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
 

Is it epilepsy?

Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.

In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.

The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.

By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.

However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.

Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.

Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.

However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
 

Don’t miss those ticks

Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.

The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.

Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.

Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.

Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.

“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.

Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

VANCOUVER – In contrast to some previous research, investigators found no significant correlation between common biologic and oral small molecule treatments for inflammatory bowel disease (IBD) and an increased risk of major adverse cardiovascular events (MACE).

In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, and ustekinumab not only did not increase risk, but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.

Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.

“The decrease in MACE with biologics was significant – and a bit surprising – but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.

“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told this news organization.

The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Dr. Regueiro reported at the ACG: American College of Gastroenterology annual scientific meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”
 

Therapies previously implicated in increased MACE risk

IBD itself is associated with increased MACE risk, likely because of chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.

The Oral Surveillance postmarketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs. a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.

While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Dr. Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.

The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3,194 adults with IBD taking an oral small molecule treatment vs. another 3,194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large U.S. claims database that includes millions of patients.
 

Key findings

The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio, 0.69; 95% confidence interval, 0.66-0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI, 0.61-0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65-0.77; P < .0001), compared with IBD patients not on biological therapy.

The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI, 0.81-0.89; P < .0001).

Dr. Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”

IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82-1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI, 0.60-1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57-1.33; P = .5148).

In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83-1.39; P = .5957).

All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.

Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.
 

Difference in IBD and rheumatoid arthritis populations

The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”

Dr. Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”

“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”

“There are probably some high-risk populations that we still want to be careful with,” added Dr. Leighton, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients – and it’s a good thing because these drugs work very well.”

The study was independently supported. Lead author Dr. Qapaja had no relevant financial relationships. Dr. Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves in these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Dr. Leighton is an advisory committee/board member for Braintree.

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

VANCOUVER – In contrast to some previous research, investigators found no significant correlation between common biologic and oral small molecule treatments for inflammatory bowel disease (IBD) and an increased risk of major adverse cardiovascular events (MACE).

In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, and ustekinumab not only did not increase risk, but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.

Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.

“The decrease in MACE with biologics was significant – and a bit surprising – but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.

“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told this news organization.

The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Dr. Regueiro reported at the ACG: American College of Gastroenterology annual scientific meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”
 

Therapies previously implicated in increased MACE risk

IBD itself is associated with increased MACE risk, likely because of chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.

The Oral Surveillance postmarketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs. a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.

While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Dr. Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.

The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3,194 adults with IBD taking an oral small molecule treatment vs. another 3,194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large U.S. claims database that includes millions of patients.
 

Key findings

The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio, 0.69; 95% confidence interval, 0.66-0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI, 0.61-0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65-0.77; P < .0001), compared with IBD patients not on biological therapy.

The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI, 0.81-0.89; P < .0001).

Dr. Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”

IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82-1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI, 0.60-1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57-1.33; P = .5148).

In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83-1.39; P = .5957).

All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.

Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.
 

Difference in IBD and rheumatoid arthritis populations

The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”

Dr. Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”

“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”

“There are probably some high-risk populations that we still want to be careful with,” added Dr. Leighton, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients – and it’s a good thing because these drugs work very well.”

The study was independently supported. Lead author Dr. Qapaja had no relevant financial relationships. Dr. Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves in these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Dr. Leighton is an advisory committee/board member for Braintree.

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

VANCOUVER – In contrast to some previous research, investigators found no significant correlation between common biologic and oral small molecule treatments for inflammatory bowel disease (IBD) and an increased risk of major adverse cardiovascular events (MACE).

In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, and ustekinumab not only did not increase risk, but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.

Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.

“The decrease in MACE with biologics was significant – and a bit surprising – but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.

“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told this news organization.

The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Dr. Regueiro reported at the ACG: American College of Gastroenterology annual scientific meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”
 

Therapies previously implicated in increased MACE risk

IBD itself is associated with increased MACE risk, likely because of chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.

The Oral Surveillance postmarketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs. a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.

While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Dr. Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.

The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3,194 adults with IBD taking an oral small molecule treatment vs. another 3,194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large U.S. claims database that includes millions of patients.
 

Key findings

The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio, 0.69; 95% confidence interval, 0.66-0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI, 0.61-0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65-0.77; P < .0001), compared with IBD patients not on biological therapy.

The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI, 0.81-0.89; P < .0001).

Dr. Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”

IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82-1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI, 0.60-1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57-1.33; P = .5148).

In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83-1.39; P = .5957).

All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.

Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.
 

Difference in IBD and rheumatoid arthritis populations

The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”

Dr. Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”

“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”

“There are probably some high-risk populations that we still want to be careful with,” added Dr. Leighton, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients – and it’s a good thing because these drugs work very well.”

The study was independently supported. Lead author Dr. Qapaja had no relevant financial relationships. Dr. Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves in these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Dr. Leighton is an advisory committee/board member for Braintree.

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

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

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

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

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

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

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