The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival.  J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046

A new drug application for berdazimer gel 10.3% for treating molluscum contagiosum (MC) has been submitted to the Food and Drug Administration, the manufacturer announced.

If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.

The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.

The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.

The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.

A new drug application for berdazimer gel 10.3% for treating molluscum contagiosum (MC) has been submitted to the Food and Drug Administration, the manufacturer announced.

If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.

The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.

The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.

The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.

A new drug application for berdazimer gel 10.3% for treating molluscum contagiosum (MC) has been submitted to the Food and Drug Administration, the manufacturer announced.

If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.

The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.

The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.

The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

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

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

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

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

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

Researchers have found a genetic link between the risk for COVID-19 infection and the leading cause of vision loss among people age 50 and older, age-related macular degeneration. 

The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.

Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands. 

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.

Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.

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

Researchers have found a genetic link between the risk for COVID-19 infection and the leading cause of vision loss among people age 50 and older, age-related macular degeneration. 

The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.

Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands. 

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.

Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.

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

Researchers have found a genetic link between the risk for COVID-19 infection and the leading cause of vision loss among people age 50 and older, age-related macular degeneration. 

The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.

Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands. 

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.

Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.

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

Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.

In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.

Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.

“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”

The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), and three strata of obesity – obese I (30 to <35 kg/m²), obese II (35 to <40 kg/m²), and obese III (>40 kg/m²).

For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.

For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.

Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.

For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.

Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.

Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.

FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.

Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.

Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.

“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”

The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.

Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.

In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.

Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.

“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”

The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), and three strata of obesity – obese I (30 to <35 kg/m²), obese II (35 to <40 kg/m²), and obese III (>40 kg/m²).

For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.

For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.

Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.

For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.

Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.

Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.

FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.

Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.

Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.

“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”

The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.

Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.

In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.

Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.

“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”

The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), and three strata of obesity – obese I (30 to <35 kg/m²), obese II (35 to <40 kg/m²), and obese III (>40 kg/m²).

For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.

For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.

Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.

For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.

Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.

Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.

FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.

Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.

Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.

“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”

The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.

Individuals with schizophrenia showed larger discrepancies between actual and ideal positive affect, compared with healthy controls, in contrast to the investigators’ hypothesis in a study of 61 individuals.

Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.

Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.

In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.

The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.

Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.

Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.

The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.

However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.

The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.

Individuals with schizophrenia showed larger discrepancies between actual and ideal positive affect, compared with healthy controls, in contrast to the investigators’ hypothesis in a study of 61 individuals.

Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.

Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.

In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.

The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.

Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.

Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.

The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.

However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.

The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.

Individuals with schizophrenia showed larger discrepancies between actual and ideal positive affect, compared with healthy controls, in contrast to the investigators’ hypothesis in a study of 61 individuals.

Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.

Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.

In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.

The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.

Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.

Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.

The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.

However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.

The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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