Liam Davenport

MILAN – Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive multiple sclerosis (MS), suggest results from two clinical trials.

For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).

After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.

The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.

The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).

Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Anti-CD20–naive

OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.

They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.

In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.

The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.

By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.

The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.

However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.

Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”

He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
 

Efficacy maintained

The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.

After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.

Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.

The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.

At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.

The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.

They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
 

Reassuring results

“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.

“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.

“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.

“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.

In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”

OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.

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

MILAN – Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive multiple sclerosis (MS), suggest results from two clinical trials.

For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).

After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.

The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.

The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).

Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Anti-CD20–naive

OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.

They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.

In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.

The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.

By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.

The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.

However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.

Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”

He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
 

Efficacy maintained

The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.

After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.

Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.

The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.

At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.

The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.

They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
 

Reassuring results

“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.

“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.

“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.

“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.

In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”

OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.

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

MILAN – Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive multiple sclerosis (MS), suggest results from two clinical trials.

For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).

After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.

The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.

The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).

Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Anti-CD20–naive

OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.

They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.

In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.

The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.

By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.

The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.

However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.

Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”

He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
 

Efficacy maintained

The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.

After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.

Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.

The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.

At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.

The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.

They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
 

Reassuring results

“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.

“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.

“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.

“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.

In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”

OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.

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

BARCELONA – The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density, new imaging data suggest.

In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.

The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.

First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.

“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
 

Marked increase in synaptic density

SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.

For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.

They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.

Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.

When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).

However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.

Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).

In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.

“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
 

Exciting but not conclusive

Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.

“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.

Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.

Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.

Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”

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

BARCELONA – The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density, new imaging data suggest.

In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.

The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.

First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.

“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
 

Marked increase in synaptic density

SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.

For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.

They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.

Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.

When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).

However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.

Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).

In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.

“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
 

Exciting but not conclusive

Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.

“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.

Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.

Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.

Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”

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

BARCELONA – The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density, new imaging data suggest.

In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.

The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.

First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.

“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
 

Marked increase in synaptic density

SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.

For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.

They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.

Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.

When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).

However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.

Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).

In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.

“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
 

Exciting but not conclusive

Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.

“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.

Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.

Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.

Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”

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

MADRID – “Why did I choose this?”

That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.

“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.

This oncologist is hardly alone.

Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.

A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.

This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.

More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.

Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.

The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.

Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.

Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.

Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.

“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.

While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.

In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.

A panel of experts at the meeting touched on some of these solutions.

Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.

Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.

“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”

The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.

However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”

But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”

In other words, oncologists need to be able to set boundaries and say no.

Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.

Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.

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

MADRID – “Why did I choose this?”

That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.

“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.

This oncologist is hardly alone.

Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.

A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.

This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.

More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.

Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.

The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.

Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.

Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.

Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.

“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.

While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.

In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.

A panel of experts at the meeting touched on some of these solutions.

Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.

Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.

“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”

The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.

However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”

But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”

In other words, oncologists need to be able to set boundaries and say no.

Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.

Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.

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

MADRID – “Why did I choose this?”

That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.

“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.

This oncologist is hardly alone.

Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.

A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.

This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.

More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.

Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.

The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.

Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.

Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.

Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.

“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.

While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.

In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.

A panel of experts at the meeting touched on some of these solutions.

Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.

Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.

“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”

The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.

However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”

But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”

In other words, oncologists need to be able to set boundaries and say no.

Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.

Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.

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

MILAN – A specially adapted frame to support individuals with walking and balance disabilities could help people with multiple sclerosis engage in moderate to vigorous physical activity and improve their physical function, a pilot study suggests.

“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.

Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.

“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.

It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
 

Dearth of exercise opportunities

The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.

This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”

In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.

The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.

The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.

The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
 

The camaraderie of physical activity

With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.

The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).

There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.

A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.

The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
 

Mix of physical interventions

Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.

He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”

However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”

With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”

Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.

Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”

The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.

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

MILAN – A specially adapted frame to support individuals with walking and balance disabilities could help people with multiple sclerosis engage in moderate to vigorous physical activity and improve their physical function, a pilot study suggests.

“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.

Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.

“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.

It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
 

Dearth of exercise opportunities

The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.

This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”

In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.

The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.

The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.

The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
 

The camaraderie of physical activity

With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.

The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).

There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.

A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.

The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
 

Mix of physical interventions

Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.

He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”

However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”

With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”

Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.

Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”

The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.

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

MILAN – A specially adapted frame to support individuals with walking and balance disabilities could help people with multiple sclerosis engage in moderate to vigorous physical activity and improve their physical function, a pilot study suggests.

“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.

Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.

“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.

It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
 

Dearth of exercise opportunities

The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.

This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”

In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.

The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.

The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.

The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
 

The camaraderie of physical activity

With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.

The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).

There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.

A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.

The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
 

Mix of physical interventions

Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.

He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”

However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”

With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”

Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.

Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”

The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.

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

BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.

The research was presented at the annual congress of the European Academy of Dermatology and Venereology.

More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.

“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.

“For me, this is proof of concept for so many things, and it gets me very excited.”

Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”

He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”

Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.

Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”

Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”

He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”

At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.

Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.

Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”

To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.

Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.

The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.

Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.

Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.

The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.

By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).

Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.

There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.

The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).

Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.

A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.

Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.

Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.

The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.

The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.

Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.

A version of this article appeared on Medscape.com.

BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.

The research was presented at the annual congress of the European Academy of Dermatology and Venereology.

More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.

“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.

“For me, this is proof of concept for so many things, and it gets me very excited.”

Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”

He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”

Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.

Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”

Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”

He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”

At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.

Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.

Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”

To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.

Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.

The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.

Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.

Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.

The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.

By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).

Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.

There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.

The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).

Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.

A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.

Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.

Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.

The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.

The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.

Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.

A version of this article appeared on Medscape.com.

BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.

The research was presented at the annual congress of the European Academy of Dermatology and Venereology.

More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.

“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.

“For me, this is proof of concept for so many things, and it gets me very excited.”

Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”

He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”

Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.

Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”

Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”

He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”

At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.

Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.

Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”

To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.

Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.

The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.

Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.

Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.

The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.

By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).

Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.

There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.

The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).

Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.

A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.

Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.

Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.

The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.

The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.

Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.

A version of this article appeared on Medscape.com.

MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.

In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.

Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.

In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.

The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.

Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.

However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
 

Inside AtTEnd

A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.

David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”

The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.

This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.

To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.

Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.

The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.

The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.

Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.

In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).

A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.

Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).

Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”

Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.

But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
 

Inside DUO-E

The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.

The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.

Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.

Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.

About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.

Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).

This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).

In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).

Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).

However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.

Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.

But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.

“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”

So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.

AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.

DUO-E was funded by AstraZeneca.

Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.

Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.

Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.

Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.

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

MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.

In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.

Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.

In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.

The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.

Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.

However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
 

Inside AtTEnd

A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.

David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”

The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.

This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.

To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.

Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.

The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.

The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.

Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.

In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).

A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.

Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).

Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”

Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.

But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
 

Inside DUO-E

The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.

The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.

Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.

Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.

About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.

Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).

This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).

In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).

Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).

However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.

Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.

But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.

“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”

So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.

AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.

DUO-E was funded by AstraZeneca.

Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.

Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.

Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.

Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.

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

MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.

In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.

Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.

In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.

The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.

Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.

However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
 

Inside AtTEnd

A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.

David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”

The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.

This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.

To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.

Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.

The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.

The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.

Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.

In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).

A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.

Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).

Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”

Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.

But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
 

Inside DUO-E

The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.

The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.

Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.

Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.

About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.

Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).

This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).

In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).

Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).

However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.

Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.

But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.

“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”

So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.

AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.

DUO-E was funded by AstraZeneca.

Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.

Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.

Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.

Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.

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

MILAN – A tool kit combining a wearable device with automated algorithms allows for the passive monitoring of disease parameters in people with multiple sclerosis (MS) and may even be able to predict the course of the disease, suggests a pilot study.

Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.

The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.

Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Leveraging big data to improve outcomes

The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.

For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.

Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.

To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.

This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
 

Feasible with high levels of confidence

Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.

The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.

The team reports that the data from the tool kit “are in line with those reported in the literature.”

It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.

Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.

The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.

Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.

They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
 

Reducing daily step count

Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”

She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.

“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”

The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.

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

MILAN – A tool kit combining a wearable device with automated algorithms allows for the passive monitoring of disease parameters in people with multiple sclerosis (MS) and may even be able to predict the course of the disease, suggests a pilot study.

Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.

The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.

Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Leveraging big data to improve outcomes

The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.

For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.

Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.

To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.

This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
 

Feasible with high levels of confidence

Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.

The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.

The team reports that the data from the tool kit “are in line with those reported in the literature.”

It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.

Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.

The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.

Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.

They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
 

Reducing daily step count

Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”

She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.

“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”

The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.

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

MILAN – A tool kit combining a wearable device with automated algorithms allows for the passive monitoring of disease parameters in people with multiple sclerosis (MS) and may even be able to predict the course of the disease, suggests a pilot study.

Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.

The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.

Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Leveraging big data to improve outcomes

The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.

For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.

Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.

To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.

This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
 

Feasible with high levels of confidence

Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.

The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.

The team reports that the data from the tool kit “are in line with those reported in the literature.”

It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.

Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.

The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.

Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.

They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
 

Reducing daily step count

Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”

She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.

“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”

The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.

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

MADRID – More than one-third of patients with locally advanced esophageal cancer who have a complete clinical response to neoadjuvant chemoradiotherapy may be able to safely avoid major surgery, findings from the Dutch SANO trial suggest.

After 2 years, researchers found no significant differences in overall and disease-free survival between patients on active surveillance and those who received surgery either immediately following neoadjuvant chemoradiotherapy or who switched from active surveillance to surgery.

Overall, patients who underwent active surveillance had “noninferior overall survival at 2 years,” said Berend J. Van der Wilk, PhD candidate, Erasmus University, Rotterdam, the Netherlands, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Over the 2-year follow-up, at least 35% of patients on active surveillance were spared surgery. Patients on active surveillance who experienced locoregional regrowth could still undergo surgery, Mr. Van der Wilk said.

Magnus Nilsson, MD, PhD, the invited discussant, who was not involved in the research, said performing such a conceptually important and complex trial was a “huge achievement.” However, Dr. Nilsson highlighted some “major concerns” with the trial design, which could affect the generalizability of the findings.

Avoiding surgery?

Esophagectomy remains the “keystone of curative treatment for esophageal cancer,” Mr. Van der Wilks explained. However, this operation is a “major surgical procedure” that comes with a mortality rate of up to 5%. As many as 59% of patients experience complications.

The CROSS trial, which included more than 360 patients with esophageal or esophagogastric junction cancer, found that neoadjuvant chemoradiotherapy improved survival among patients with potentially curable disease; 29% of patients achieved a pathologic complete response.

Mr. Van der Wilk said those strong outcomes create some uncertainty as to whether all patients need standard surgery after chemoradiotherapy.

In other words, Mr. Van der Wilk asked, “Should we be willing to follow an active surveillance, organ-sparing strategy for patients with a clinical response?”

An active surveillance strategy, he said, would require frequent evaluations of the patient’s clinical response. Surgery would be performed only in cases of proven residual tumor in which there were no distant metastases. The potential pitfall of an active surveillance approach is that patients may develop unresectable tumor regrowths, “possibly resulting in inferior overall survival.”

To compare active surveillance with standard surgery, the team conducted a phase 3 noninferiority stepped-wedge cluster randomized trial involving patients with locally advanced esophageal cancer.

Patients received neoadjuvant chemoradiotherapy with carboplatin and paclitaxel for 5 weeks. Concurrent radiotherapy was delivered at 41.4 Gy in 23 fractions, 5 days per week, as in the CROSS trial.

More than 300 patients who achieved a complete clinical response 12 weeks after completing chemoradiotherapy were randomly assigned to undergo standard surgery or active surveillance. Surgery was performed for those with subsequent tumor regrowth.

Overall, 198 patients underwent active surveillance, and 111 patients underwent standard surgery. The two groups were well balanced in terms of median age, sex distribution, proportion of adenocarcinomas, and World Health Organization performance scores. At the last patient assessment, on July 6, 2023, the median follow-up was 38 months.

Overall, 101 of 111 patients in the standard surgery arm and 83 of 198 (42%) in the active surveillance group had surgery. The time to surgery in the active surveillance arm was 5.9 months, compared with 0.7 months with standard surgery. For both groups, the R0 resection rate was 98%.

Mr. Van der Wilk reported no significant difference in overall survival between the active surveillance and standard surgery groups (hazard ratio for death, 1.14; 95% confidence interval, 0.74-0.78; P = .55). Overall survival in the active surveillance group was noninferior to that in the standard surgery group at 2 years. Noninferiority was defined as an overall survival difference between the two arms of less than 15%.

Mr. Van der Wilk also reported no significant difference in disease-free survival between the active surveillance and the standard surgery groups – 35 months with active surveillance, and 49 months with surgery (HR, 1.35; P = .15). At 30 months following neoadjuvant chemoradiotherapy, 43% of patients on active surveillance and 34% with standard surgery developed distant metastases, but the difference was not significant (odds ratio, 1.45; P = .18).

Among the patients in the active surveillance arm who had a complete response, 35% (n = 69) had a persistent clinical response, while 17% (33 patients) developed distant metastases, and 48% (n = 96) experienced locoregional growth. The postoperative 90-day mortality was 4% in the active surveillance group and 5% in the surgery group.

Health-related quality of life was significantly better at 6 and 9 months in the active surveillance group, Mr. Van der Wilk noted.

Although Dr. Nilsson, the invited discussant, highlighted the importance of the trial, he also expressed concern over the trial design.

The intention-to-treat analysis was contaminated, Dr. Nilsson said, because the trial design allowed for one crossover, but patients in the trial crossed over at two time points – 35 patients who were initially assigned to standard surgery crossed over to the active surveillance arm, and later, seven patients from a preSANO trial were included in the active surveillance arm.

Dr. Nilsson also expressed concern about mixing squamous cell carcinoma and adenocarcinoma histologies in the study. If the authors had distinguished patients with squamous cell carcinoma and those with adenocarcinoma in each arm, there may have a difference in overall survival, given that squamous cell carcinoma is much easier to treat.

The study also included some patients who did not have a complete clinical response and whose surgery was delayed by more than 10 weeks – a practice that, Dr. Nilsson said, “does not really seem to be safe.” A recent study led by Dr. Nilsson found that delaying surgery for 10-12 weeks in comparison with 4-6 weeks did not improve histologic complete response or other pathologic endpoints and may have led to worse survival.

“I’m afraid it’s not really certain that it’s safe to prolong surgery more than 10 weeks or longer in the clinical noncomplete responders,” said Dr. Nilsson, from the department of clinical science, intervention, and technology, Karolinska Institute, Stockholm.

Overall, he said, the study “suggests that survival may be noninferior” among patients on active surveillance in comparison with those who undergo immediate surgery, but the findings need to be confirmed in a trial with a more stringent intention-to-treat analysis that is stratified by histologic subtypes.

The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development (ZonMw). Mr. Van der Wilk has disclosed no relevant financial relationships. Dr. Nilsson has relationships with Medtronic, Intuitive Surgical, Bristol-Myers Squibb, and Merck Sharp & Dohme, from which he received no personal financial benefit.

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

MADRID – More than one-third of patients with locally advanced esophageal cancer who have a complete clinical response to neoadjuvant chemoradiotherapy may be able to safely avoid major surgery, findings from the Dutch SANO trial suggest.

After 2 years, researchers found no significant differences in overall and disease-free survival between patients on active surveillance and those who received surgery either immediately following neoadjuvant chemoradiotherapy or who switched from active surveillance to surgery.

Overall, patients who underwent active surveillance had “noninferior overall survival at 2 years,” said Berend J. Van der Wilk, PhD candidate, Erasmus University, Rotterdam, the Netherlands, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Over the 2-year follow-up, at least 35% of patients on active surveillance were spared surgery. Patients on active surveillance who experienced locoregional regrowth could still undergo surgery, Mr. Van der Wilk said.

Magnus Nilsson, MD, PhD, the invited discussant, who was not involved in the research, said performing such a conceptually important and complex trial was a “huge achievement.” However, Dr. Nilsson highlighted some “major concerns” with the trial design, which could affect the generalizability of the findings.

Avoiding surgery?

Esophagectomy remains the “keystone of curative treatment for esophageal cancer,” Mr. Van der Wilks explained. However, this operation is a “major surgical procedure” that comes with a mortality rate of up to 5%. As many as 59% of patients experience complications.

The CROSS trial, which included more than 360 patients with esophageal or esophagogastric junction cancer, found that neoadjuvant chemoradiotherapy improved survival among patients with potentially curable disease; 29% of patients achieved a pathologic complete response.

Mr. Van der Wilk said those strong outcomes create some uncertainty as to whether all patients need standard surgery after chemoradiotherapy.

In other words, Mr. Van der Wilk asked, “Should we be willing to follow an active surveillance, organ-sparing strategy for patients with a clinical response?”

An active surveillance strategy, he said, would require frequent evaluations of the patient’s clinical response. Surgery would be performed only in cases of proven residual tumor in which there were no distant metastases. The potential pitfall of an active surveillance approach is that patients may develop unresectable tumor regrowths, “possibly resulting in inferior overall survival.”

To compare active surveillance with standard surgery, the team conducted a phase 3 noninferiority stepped-wedge cluster randomized trial involving patients with locally advanced esophageal cancer.

Patients received neoadjuvant chemoradiotherapy with carboplatin and paclitaxel for 5 weeks. Concurrent radiotherapy was delivered at 41.4 Gy in 23 fractions, 5 days per week, as in the CROSS trial.

More than 300 patients who achieved a complete clinical response 12 weeks after completing chemoradiotherapy were randomly assigned to undergo standard surgery or active surveillance. Surgery was performed for those with subsequent tumor regrowth.

Overall, 198 patients underwent active surveillance, and 111 patients underwent standard surgery. The two groups were well balanced in terms of median age, sex distribution, proportion of adenocarcinomas, and World Health Organization performance scores. At the last patient assessment, on July 6, 2023, the median follow-up was 38 months.

Overall, 101 of 111 patients in the standard surgery arm and 83 of 198 (42%) in the active surveillance group had surgery. The time to surgery in the active surveillance arm was 5.9 months, compared with 0.7 months with standard surgery. For both groups, the R0 resection rate was 98%.

Mr. Van der Wilk reported no significant difference in overall survival between the active surveillance and standard surgery groups (hazard ratio for death, 1.14; 95% confidence interval, 0.74-0.78; P = .55). Overall survival in the active surveillance group was noninferior to that in the standard surgery group at 2 years. Noninferiority was defined as an overall survival difference between the two arms of less than 15%.

Mr. Van der Wilk also reported no significant difference in disease-free survival between the active surveillance and the standard surgery groups – 35 months with active surveillance, and 49 months with surgery (HR, 1.35; P = .15). At 30 months following neoadjuvant chemoradiotherapy, 43% of patients on active surveillance and 34% with standard surgery developed distant metastases, but the difference was not significant (odds ratio, 1.45; P = .18).

Among the patients in the active surveillance arm who had a complete response, 35% (n = 69) had a persistent clinical response, while 17% (33 patients) developed distant metastases, and 48% (n = 96) experienced locoregional growth. The postoperative 90-day mortality was 4% in the active surveillance group and 5% in the surgery group.

Health-related quality of life was significantly better at 6 and 9 months in the active surveillance group, Mr. Van der Wilk noted.

Although Dr. Nilsson, the invited discussant, highlighted the importance of the trial, he also expressed concern over the trial design.

The intention-to-treat analysis was contaminated, Dr. Nilsson said, because the trial design allowed for one crossover, but patients in the trial crossed over at two time points – 35 patients who were initially assigned to standard surgery crossed over to the active surveillance arm, and later, seven patients from a preSANO trial were included in the active surveillance arm.

Dr. Nilsson also expressed concern about mixing squamous cell carcinoma and adenocarcinoma histologies in the study. If the authors had distinguished patients with squamous cell carcinoma and those with adenocarcinoma in each arm, there may have a difference in overall survival, given that squamous cell carcinoma is much easier to treat.

The study also included some patients who did not have a complete clinical response and whose surgery was delayed by more than 10 weeks – a practice that, Dr. Nilsson said, “does not really seem to be safe.” A recent study led by Dr. Nilsson found that delaying surgery for 10-12 weeks in comparison with 4-6 weeks did not improve histologic complete response or other pathologic endpoints and may have led to worse survival.

“I’m afraid it’s not really certain that it’s safe to prolong surgery more than 10 weeks or longer in the clinical noncomplete responders,” said Dr. Nilsson, from the department of clinical science, intervention, and technology, Karolinska Institute, Stockholm.

Overall, he said, the study “suggests that survival may be noninferior” among patients on active surveillance in comparison with those who undergo immediate surgery, but the findings need to be confirmed in a trial with a more stringent intention-to-treat analysis that is stratified by histologic subtypes.

The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development (ZonMw). Mr. Van der Wilk has disclosed no relevant financial relationships. Dr. Nilsson has relationships with Medtronic, Intuitive Surgical, Bristol-Myers Squibb, and Merck Sharp & Dohme, from which he received no personal financial benefit.

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

MADRID – More than one-third of patients with locally advanced esophageal cancer who have a complete clinical response to neoadjuvant chemoradiotherapy may be able to safely avoid major surgery, findings from the Dutch SANO trial suggest.

After 2 years, researchers found no significant differences in overall and disease-free survival between patients on active surveillance and those who received surgery either immediately following neoadjuvant chemoradiotherapy or who switched from active surveillance to surgery.

Overall, patients who underwent active surveillance had “noninferior overall survival at 2 years,” said Berend J. Van der Wilk, PhD candidate, Erasmus University, Rotterdam, the Netherlands, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Over the 2-year follow-up, at least 35% of patients on active surveillance were spared surgery. Patients on active surveillance who experienced locoregional regrowth could still undergo surgery, Mr. Van der Wilk said.

Magnus Nilsson, MD, PhD, the invited discussant, who was not involved in the research, said performing such a conceptually important and complex trial was a “huge achievement.” However, Dr. Nilsson highlighted some “major concerns” with the trial design, which could affect the generalizability of the findings.

Avoiding surgery?

Esophagectomy remains the “keystone of curative treatment for esophageal cancer,” Mr. Van der Wilks explained. However, this operation is a “major surgical procedure” that comes with a mortality rate of up to 5%. As many as 59% of patients experience complications.

The CROSS trial, which included more than 360 patients with esophageal or esophagogastric junction cancer, found that neoadjuvant chemoradiotherapy improved survival among patients with potentially curable disease; 29% of patients achieved a pathologic complete response.

Mr. Van der Wilk said those strong outcomes create some uncertainty as to whether all patients need standard surgery after chemoradiotherapy.

In other words, Mr. Van der Wilk asked, “Should we be willing to follow an active surveillance, organ-sparing strategy for patients with a clinical response?”

An active surveillance strategy, he said, would require frequent evaluations of the patient’s clinical response. Surgery would be performed only in cases of proven residual tumor in which there were no distant metastases. The potential pitfall of an active surveillance approach is that patients may develop unresectable tumor regrowths, “possibly resulting in inferior overall survival.”

To compare active surveillance with standard surgery, the team conducted a phase 3 noninferiority stepped-wedge cluster randomized trial involving patients with locally advanced esophageal cancer.

Patients received neoadjuvant chemoradiotherapy with carboplatin and paclitaxel for 5 weeks. Concurrent radiotherapy was delivered at 41.4 Gy in 23 fractions, 5 days per week, as in the CROSS trial.

More than 300 patients who achieved a complete clinical response 12 weeks after completing chemoradiotherapy were randomly assigned to undergo standard surgery or active surveillance. Surgery was performed for those with subsequent tumor regrowth.

Overall, 198 patients underwent active surveillance, and 111 patients underwent standard surgery. The two groups were well balanced in terms of median age, sex distribution, proportion of adenocarcinomas, and World Health Organization performance scores. At the last patient assessment, on July 6, 2023, the median follow-up was 38 months.

Overall, 101 of 111 patients in the standard surgery arm and 83 of 198 (42%) in the active surveillance group had surgery. The time to surgery in the active surveillance arm was 5.9 months, compared with 0.7 months with standard surgery. For both groups, the R0 resection rate was 98%.

Mr. Van der Wilk reported no significant difference in overall survival between the active surveillance and standard surgery groups (hazard ratio for death, 1.14; 95% confidence interval, 0.74-0.78; P = .55). Overall survival in the active surveillance group was noninferior to that in the standard surgery group at 2 years. Noninferiority was defined as an overall survival difference between the two arms of less than 15%.

Mr. Van der Wilk also reported no significant difference in disease-free survival between the active surveillance and the standard surgery groups – 35 months with active surveillance, and 49 months with surgery (HR, 1.35; P = .15). At 30 months following neoadjuvant chemoradiotherapy, 43% of patients on active surveillance and 34% with standard surgery developed distant metastases, but the difference was not significant (odds ratio, 1.45; P = .18).

Among the patients in the active surveillance arm who had a complete response, 35% (n = 69) had a persistent clinical response, while 17% (33 patients) developed distant metastases, and 48% (n = 96) experienced locoregional growth. The postoperative 90-day mortality was 4% in the active surveillance group and 5% in the surgery group.

Health-related quality of life was significantly better at 6 and 9 months in the active surveillance group, Mr. Van der Wilk noted.

Although Dr. Nilsson, the invited discussant, highlighted the importance of the trial, he also expressed concern over the trial design.

The intention-to-treat analysis was contaminated, Dr. Nilsson said, because the trial design allowed for one crossover, but patients in the trial crossed over at two time points – 35 patients who were initially assigned to standard surgery crossed over to the active surveillance arm, and later, seven patients from a preSANO trial were included in the active surveillance arm.

Dr. Nilsson also expressed concern about mixing squamous cell carcinoma and adenocarcinoma histologies in the study. If the authors had distinguished patients with squamous cell carcinoma and those with adenocarcinoma in each arm, there may have a difference in overall survival, given that squamous cell carcinoma is much easier to treat.

The study also included some patients who did not have a complete clinical response and whose surgery was delayed by more than 10 weeks – a practice that, Dr. Nilsson said, “does not really seem to be safe.” A recent study led by Dr. Nilsson found that delaying surgery for 10-12 weeks in comparison with 4-6 weeks did not improve histologic complete response or other pathologic endpoints and may have led to worse survival.

“I’m afraid it’s not really certain that it’s safe to prolong surgery more than 10 weeks or longer in the clinical noncomplete responders,” said Dr. Nilsson, from the department of clinical science, intervention, and technology, Karolinska Institute, Stockholm.

Overall, he said, the study “suggests that survival may be noninferior” among patients on active surveillance in comparison with those who undergo immediate surgery, but the findings need to be confirmed in a trial with a more stringent intention-to-treat analysis that is stratified by histologic subtypes.

The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development (ZonMw). Mr. Van der Wilk has disclosed no relevant financial relationships. Dr. Nilsson has relationships with Medtronic, Intuitive Surgical, Bristol-Myers Squibb, and Merck Sharp & Dohme, from which he received no personal financial benefit.

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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