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Insulin Resistance Doesn’t Affect Finerenone’s Efficacy
TOPLINE:
In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone.
METHODOLOGY:
- Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
- This post hoc analysis of FIDELITY, a pooled analysis of the and trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
- An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
- Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).
TAKEAWAY:
- The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
- The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
- The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
- The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.
IN PRACTICE:
“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.
SOURCE:
This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.
LIMITATIONS:
This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.
DISCLOSURES:
The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.
A version of this article appeared on Medscape.com.
TOPLINE:
In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone.
METHODOLOGY:
- Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
- This post hoc analysis of FIDELITY, a pooled analysis of the and trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
- An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
- Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).
TAKEAWAY:
- The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
- The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
- The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
- The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.
IN PRACTICE:
“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.
SOURCE:
This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.
LIMITATIONS:
This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.
DISCLOSURES:
The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.
A version of this article appeared on Medscape.com.
TOPLINE:
In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone.
METHODOLOGY:
- Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
- This post hoc analysis of FIDELITY, a pooled analysis of the and trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
- An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
- Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).
TAKEAWAY:
- The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
- The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
- The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
- The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.
IN PRACTICE:
“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.
SOURCE:
This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.
LIMITATIONS:
This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.
DISCLOSURES:
The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.
A version of this article appeared on Medscape.com.
Etrasimod Appears Effective in Eosinophilic Esophagitis: Phase 2 Study
Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
Prospect of Another EoE Treatment
In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”
The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.
“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.
The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.
“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”
In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.
“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.
Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.
Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
Prospect of Another EoE Treatment
In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”
The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.
“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.
The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.
“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”
In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.
“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.
Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.
Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
Prospect of Another EoE Treatment
In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”
The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.
“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.
The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.
“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”
In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.
“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.
Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.
FROM ACG 2023
Medical Aid in Dying Should Be Legal, Says Ethicist
This transcript has been edited for clarity.
Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine.
Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.
Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.
There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.
One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.
New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.
If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.
The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.
The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.
You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.
Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.
Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.
I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.
Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.
I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.
I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.
Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:
- Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
- Serves as a contributing author and adviser for: Medscape
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine.
Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.
Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.
There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.
One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.
New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.
If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.
The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.
The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.
You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.
Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.
Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.
I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.
Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.
I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.
I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.
Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:
- Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
- Serves as a contributing author and adviser for: Medscape
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine.
Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.
Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.
There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.
One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.
New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.
If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.
The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.
The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.
You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.
Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.
Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.
I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.
Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.
I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.
I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.
Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:
- Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
- Serves as a contributing author and adviser for: Medscape
A version of this article appeared on Medscape.com.
The Emerging Physician-Scientist Crisis in America
Recent reporting has shown that That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.
So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?
Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.
The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.
Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.
Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.
Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.
The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.
Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.
Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Recent reporting has shown that That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.
So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?
Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.
The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.
Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.
Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.
Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.
The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.
Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.
Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Recent reporting has shown that That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.
So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?
Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.
The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.
Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.
Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.
Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.
The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.
Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.
Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Restricted Abortion Access Tied to Mental Health Harm
, which revoked a woman’s constitutional right to an abortion, new research shows.
This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.
The study was published online on January 23, 2024, in JAMA.
Mental Health Harm
In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.
The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.
The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4).
In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.
Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.
Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes.
Implications for Care
In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”
These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.
“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added.
The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.
A version of this article appeared on Medscape.com.
, which revoked a woman’s constitutional right to an abortion, new research shows.
This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.
The study was published online on January 23, 2024, in JAMA.
Mental Health Harm
In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.
The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.
The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4).
In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.
Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.
Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes.
Implications for Care
In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”
These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.
“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added.
The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.
A version of this article appeared on Medscape.com.
, which revoked a woman’s constitutional right to an abortion, new research shows.
This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.
The study was published online on January 23, 2024, in JAMA.
Mental Health Harm
In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.
The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.
The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4).
In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.
Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.
Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes.
Implications for Care
In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”
These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.
“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added.
The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.
A version of this article appeared on Medscape.com.
FROM JAMA
FDA Recommends DEA Move Cannabis From Schedule I to III
Newly released documents show that .
The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.
The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.
The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation.
Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.
“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.
In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”
Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016.
Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer.
“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
Credible Medical Use
The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.
Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted.
The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”
The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.
Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.”
Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.
“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
Opposition in Congress
It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.
“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.
The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”
The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.
He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”
“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”
A version of this article appeared on Medscape.com.
Newly released documents show that .
The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.
The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.
The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation.
Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.
“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.
In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”
Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016.
Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer.
“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
Credible Medical Use
The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.
Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted.
The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”
The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.
Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.”
Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.
“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
Opposition in Congress
It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.
“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.
The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”
The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.
He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”
“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”
A version of this article appeared on Medscape.com.
Newly released documents show that .
The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.
The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.
The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation.
Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.
“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.
In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”
Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016.
Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer.
“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
Credible Medical Use
The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.
Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted.
The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”
The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.
Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.”
Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.
“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
Opposition in Congress
It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.
“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.
The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”
The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.
He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”
“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”
A version of this article appeared on Medscape.com.
Two-Step Strategy Improves Early-Stage Ovarian Cancer Detection
TOPLINE:
a new analysis with a 21-year follow-up found.
METHODOLOGY:
- Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
- In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
- Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
- Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.
TAKEAWAY:
- Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
- Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
- Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
- The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).
IN PRACTICE:
“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.
LIMITATIONS:
This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.
SOURCE:
This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.
DISCLOSURES:
This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.
A version of this article appeared on Medscape.com.
TOPLINE:
a new analysis with a 21-year follow-up found.
METHODOLOGY:
- Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
- In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
- Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
- Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.
TAKEAWAY:
- Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
- Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
- Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
- The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).
IN PRACTICE:
“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.
LIMITATIONS:
This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.
SOURCE:
This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.
DISCLOSURES:
This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.
A version of this article appeared on Medscape.com.
TOPLINE:
a new analysis with a 21-year follow-up found.
METHODOLOGY:
- Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
- In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
- Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
- Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.
TAKEAWAY:
- Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
- Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
- Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
- The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).
IN PRACTICE:
“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.
LIMITATIONS:
This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.
SOURCE:
This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.
DISCLOSURES:
This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.
A version of this article appeared on Medscape.com.
ctDNA Clearance Improves Prediction of Relapse Risk in Urothelial Cancer
In ongoing efforts to better understand the predictive value of circulating tumor DNA (ctDNA) in cancer treatment response, new research shows ctDNA clearance following neoadjuvant treatment of muscle-invasive urothelial cancer is a better predictor of the risk of relapse than a 50% reduction in ctDNA variant allele frequency (VAF).
The combination of ctDNA with other baseline biomarkers shows further accuracy in predicting treatment response, the study also shows.
Matthew Nicholas Young, MD, of Barts Cancer Institute, London, presented the research at the ASCO Genitourinary Cancers Symposium.
“We found that ctDNA and tissue-based biomarkers improved biomarker accuracy,” Dr. Young, first author of the study, said at the meeting.
Furthermore, “ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse,” the authors said in their abstract.
“This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint,” they wrote.
Dr. Young and his colleagues have previously shown ctDNA clearance to be an important predictive marker of treatment response or relapse.
To better understand the predictive value in combination with other biomarkers, as well as whether a reduction in ctDNA variant allele frequency could be used as a surrogate predictor of relapse compared with ctDNA clearance, the authors conducted an exploratory biomarker analysis of the phase 2, multicenter ABACUS trial.
Methods and Results
In the study, 95 patients with inoperable, muscle-invasive urothelial cancer who were either not eligible for or refused neoadjuvant cisplatin-based chemotherapy, each received two cycles of atezolizumab, followed by radical cystectomy.
Previously published results show the study met its primary endpoint of a pathological complete response (pCR) of 31%, and the 2-year disease-free survival and overall survival rates were 68% and 77%, respectively.
Of the 95 patients, 40 had sequential DNA analysis that could be evaluated in the current analysis; 43% of those patients achieved a pCR, while 20% experienced a relapse.
At baseline, 63% of patients were ctDNA-positive, and after treatment, 8% achieved ctDNA clearance, while 40% had a ctDNA response of a 50% VAF reduction.
All patients who had ctDNA clearance achieved pCR and none relapsed. In comparison, 30% of patients with a 50% VAF reduction experienced relapse and only 40% achieved pCR.
In terms of correlations with baseline biomarkers, the combination of ctDNA with activated T cells was significantly associated with outcomes (P = .02), as was the combination with PDL-1 status (P = .004).
However, combination with tumor mutation burden, already weak as a predictive biomarker, remained weak when combined with ctDNA status (P = .2), Dr. Young reported.
In terms of baseline expression of ctDNA, patients who were positive at baseline showed an increase in innate and adaptive immune signaling, in a profile aligning with increased PD-L1 at baseline in ctDNA-positive patients.
In addition, decreased immune signaling was observed in ctDNA-positive patients who relapsed.
Results May Be ‘Hypothesis-Generating’
Asked during the session whether the results imply that patients with no detectable ctDNA prior to the start of therapy may not need or benefit from neoadjuvant therapy, Dr. Young said the small sample size of ctDNA patients in the study was an important limitation.
“I think [the results] are hypothesis-generating, as we know that some patients will not benefit from neoadjuvant therapy and the goal of this work is to try to identify patterns among those who may not need treatment,” he said.
Of the patients with ctDNA analysis, “only those who were ctDNA-positive at baseline relapsed, [as well as] those who were ctDNA-positive following cystectomy, so I think [the possibility that a lack of detectable ctDNA prior to the start of therapy could suggest that the patient may not need or benefit from neoadjuvant therapy] is an interesting hypothesis that has come from this work,” Dr. Young said.
Overall, the findings show that, “in ctDNA-positive patients, increased immune signals appear to be associated with better outcomes with atezolizumab,” he concluded.
“Combining immune and circulating biomarkers may be required to accurately predict response to therapy,” Dr. Young added.
The ABACUS trial was supported by Roche.
In ongoing efforts to better understand the predictive value of circulating tumor DNA (ctDNA) in cancer treatment response, new research shows ctDNA clearance following neoadjuvant treatment of muscle-invasive urothelial cancer is a better predictor of the risk of relapse than a 50% reduction in ctDNA variant allele frequency (VAF).
The combination of ctDNA with other baseline biomarkers shows further accuracy in predicting treatment response, the study also shows.
Matthew Nicholas Young, MD, of Barts Cancer Institute, London, presented the research at the ASCO Genitourinary Cancers Symposium.
“We found that ctDNA and tissue-based biomarkers improved biomarker accuracy,” Dr. Young, first author of the study, said at the meeting.
Furthermore, “ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse,” the authors said in their abstract.
“This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint,” they wrote.
Dr. Young and his colleagues have previously shown ctDNA clearance to be an important predictive marker of treatment response or relapse.
To better understand the predictive value in combination with other biomarkers, as well as whether a reduction in ctDNA variant allele frequency could be used as a surrogate predictor of relapse compared with ctDNA clearance, the authors conducted an exploratory biomarker analysis of the phase 2, multicenter ABACUS trial.
Methods and Results
In the study, 95 patients with inoperable, muscle-invasive urothelial cancer who were either not eligible for or refused neoadjuvant cisplatin-based chemotherapy, each received two cycles of atezolizumab, followed by radical cystectomy.
Previously published results show the study met its primary endpoint of a pathological complete response (pCR) of 31%, and the 2-year disease-free survival and overall survival rates were 68% and 77%, respectively.
Of the 95 patients, 40 had sequential DNA analysis that could be evaluated in the current analysis; 43% of those patients achieved a pCR, while 20% experienced a relapse.
At baseline, 63% of patients were ctDNA-positive, and after treatment, 8% achieved ctDNA clearance, while 40% had a ctDNA response of a 50% VAF reduction.
All patients who had ctDNA clearance achieved pCR and none relapsed. In comparison, 30% of patients with a 50% VAF reduction experienced relapse and only 40% achieved pCR.
In terms of correlations with baseline biomarkers, the combination of ctDNA with activated T cells was significantly associated with outcomes (P = .02), as was the combination with PDL-1 status (P = .004).
However, combination with tumor mutation burden, already weak as a predictive biomarker, remained weak when combined with ctDNA status (P = .2), Dr. Young reported.
In terms of baseline expression of ctDNA, patients who were positive at baseline showed an increase in innate and adaptive immune signaling, in a profile aligning with increased PD-L1 at baseline in ctDNA-positive patients.
In addition, decreased immune signaling was observed in ctDNA-positive patients who relapsed.
Results May Be ‘Hypothesis-Generating’
Asked during the session whether the results imply that patients with no detectable ctDNA prior to the start of therapy may not need or benefit from neoadjuvant therapy, Dr. Young said the small sample size of ctDNA patients in the study was an important limitation.
“I think [the results] are hypothesis-generating, as we know that some patients will not benefit from neoadjuvant therapy and the goal of this work is to try to identify patterns among those who may not need treatment,” he said.
Of the patients with ctDNA analysis, “only those who were ctDNA-positive at baseline relapsed, [as well as] those who were ctDNA-positive following cystectomy, so I think [the possibility that a lack of detectable ctDNA prior to the start of therapy could suggest that the patient may not need or benefit from neoadjuvant therapy] is an interesting hypothesis that has come from this work,” Dr. Young said.
Overall, the findings show that, “in ctDNA-positive patients, increased immune signals appear to be associated with better outcomes with atezolizumab,” he concluded.
“Combining immune and circulating biomarkers may be required to accurately predict response to therapy,” Dr. Young added.
The ABACUS trial was supported by Roche.
In ongoing efforts to better understand the predictive value of circulating tumor DNA (ctDNA) in cancer treatment response, new research shows ctDNA clearance following neoadjuvant treatment of muscle-invasive urothelial cancer is a better predictor of the risk of relapse than a 50% reduction in ctDNA variant allele frequency (VAF).
The combination of ctDNA with other baseline biomarkers shows further accuracy in predicting treatment response, the study also shows.
Matthew Nicholas Young, MD, of Barts Cancer Institute, London, presented the research at the ASCO Genitourinary Cancers Symposium.
“We found that ctDNA and tissue-based biomarkers improved biomarker accuracy,” Dr. Young, first author of the study, said at the meeting.
Furthermore, “ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse,” the authors said in their abstract.
“This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint,” they wrote.
Dr. Young and his colleagues have previously shown ctDNA clearance to be an important predictive marker of treatment response or relapse.
To better understand the predictive value in combination with other biomarkers, as well as whether a reduction in ctDNA variant allele frequency could be used as a surrogate predictor of relapse compared with ctDNA clearance, the authors conducted an exploratory biomarker analysis of the phase 2, multicenter ABACUS trial.
Methods and Results
In the study, 95 patients with inoperable, muscle-invasive urothelial cancer who were either not eligible for or refused neoadjuvant cisplatin-based chemotherapy, each received two cycles of atezolizumab, followed by radical cystectomy.
Previously published results show the study met its primary endpoint of a pathological complete response (pCR) of 31%, and the 2-year disease-free survival and overall survival rates were 68% and 77%, respectively.
Of the 95 patients, 40 had sequential DNA analysis that could be evaluated in the current analysis; 43% of those patients achieved a pCR, while 20% experienced a relapse.
At baseline, 63% of patients were ctDNA-positive, and after treatment, 8% achieved ctDNA clearance, while 40% had a ctDNA response of a 50% VAF reduction.
All patients who had ctDNA clearance achieved pCR and none relapsed. In comparison, 30% of patients with a 50% VAF reduction experienced relapse and only 40% achieved pCR.
In terms of correlations with baseline biomarkers, the combination of ctDNA with activated T cells was significantly associated with outcomes (P = .02), as was the combination with PDL-1 status (P = .004).
However, combination with tumor mutation burden, already weak as a predictive biomarker, remained weak when combined with ctDNA status (P = .2), Dr. Young reported.
In terms of baseline expression of ctDNA, patients who were positive at baseline showed an increase in innate and adaptive immune signaling, in a profile aligning with increased PD-L1 at baseline in ctDNA-positive patients.
In addition, decreased immune signaling was observed in ctDNA-positive patients who relapsed.
Results May Be ‘Hypothesis-Generating’
Asked during the session whether the results imply that patients with no detectable ctDNA prior to the start of therapy may not need or benefit from neoadjuvant therapy, Dr. Young said the small sample size of ctDNA patients in the study was an important limitation.
“I think [the results] are hypothesis-generating, as we know that some patients will not benefit from neoadjuvant therapy and the goal of this work is to try to identify patterns among those who may not need treatment,” he said.
Of the patients with ctDNA analysis, “only those who were ctDNA-positive at baseline relapsed, [as well as] those who were ctDNA-positive following cystectomy, so I think [the possibility that a lack of detectable ctDNA prior to the start of therapy could suggest that the patient may not need or benefit from neoadjuvant therapy] is an interesting hypothesis that has come from this work,” Dr. Young said.
Overall, the findings show that, “in ctDNA-positive patients, increased immune signals appear to be associated with better outcomes with atezolizumab,” he concluded.
“Combining immune and circulating biomarkers may be required to accurately predict response to therapy,” Dr. Young added.
The ABACUS trial was supported by Roche.
FROM ASCO GU 2024
Psychosocial burdens significant in EoE pediatric patients
Key clinical point: Diagnosis of eosinophilic esophagitis (EoE) leads to psychosocial burdens in pediatric patients, especially in patients with neurodevelopmental disorders.
Major finding: Patients with shorter disease duration (6-12 months) had a higher symptom burden (P = .03). Patients with neurodevelopmental disorders had significantly greater somatic symptoms and anxiety, lower quality of life scores, and greater sleep disordered breathing (P < .01 for all)
Study details: This study included 87 patients (age 8-18 years, mean age 12.8 years, 26% girls) who completed validated assessments of EoE symptoms, quality of life, somatization, and sleep disordered breathing during regular clinic visits. Of these, 14% had been diagnosed with a neurodevelopmental disorder.
Disclosures: The authors reported no conflicts of interest.
Source: Jensen T et al. Sleep, anxiety, somatization, quality of life, and resilience in pediatric patients with eosinophilic esophagitis. Clin Transl Gastroenterol. 2024 (Jan 11). doi: 10.14309/ctg.0000000000000672
Key clinical point: Diagnosis of eosinophilic esophagitis (EoE) leads to psychosocial burdens in pediatric patients, especially in patients with neurodevelopmental disorders.
Major finding: Patients with shorter disease duration (6-12 months) had a higher symptom burden (P = .03). Patients with neurodevelopmental disorders had significantly greater somatic symptoms and anxiety, lower quality of life scores, and greater sleep disordered breathing (P < .01 for all)
Study details: This study included 87 patients (age 8-18 years, mean age 12.8 years, 26% girls) who completed validated assessments of EoE symptoms, quality of life, somatization, and sleep disordered breathing during regular clinic visits. Of these, 14% had been diagnosed with a neurodevelopmental disorder.
Disclosures: The authors reported no conflicts of interest.
Source: Jensen T et al. Sleep, anxiety, somatization, quality of life, and resilience in pediatric patients with eosinophilic esophagitis. Clin Transl Gastroenterol. 2024 (Jan 11). doi: 10.14309/ctg.0000000000000672
Key clinical point: Diagnosis of eosinophilic esophagitis (EoE) leads to psychosocial burdens in pediatric patients, especially in patients with neurodevelopmental disorders.
Major finding: Patients with shorter disease duration (6-12 months) had a higher symptom burden (P = .03). Patients with neurodevelopmental disorders had significantly greater somatic symptoms and anxiety, lower quality of life scores, and greater sleep disordered breathing (P < .01 for all)
Study details: This study included 87 patients (age 8-18 years, mean age 12.8 years, 26% girls) who completed validated assessments of EoE symptoms, quality of life, somatization, and sleep disordered breathing during regular clinic visits. Of these, 14% had been diagnosed with a neurodevelopmental disorder.
Disclosures: The authors reported no conflicts of interest.
Source: Jensen T et al. Sleep, anxiety, somatization, quality of life, and resilience in pediatric patients with eosinophilic esophagitis. Clin Transl Gastroenterol. 2024 (Jan 11). doi: 10.14309/ctg.0000000000000672
The Breakthrough Drug Whose Full Promise Remains Unrealized
Celebrating a Decade of Sofosbuvir for Hepatitis C
Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.
Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.
The Sofosbuvir Revolution Begins
The Liver Meeting held in 2013 changed everything.
Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.
However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.
This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.
On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.
Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.
Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.
Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.
This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.
This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.
Progress, but Far From Reaching Targets
Fast-forward to 2023.
Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.
In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.
Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.
The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.
Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).
In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.
Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.
As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:
- A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
- HCV antibody testing with reflex to PCR should be used as the screening test.
- Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
- Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.
Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.
Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article appeared on Medscape.com.
Celebrating a Decade of Sofosbuvir for Hepatitis C
Celebrating a Decade of Sofosbuvir for Hepatitis C
Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.
Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.
The Sofosbuvir Revolution Begins
The Liver Meeting held in 2013 changed everything.
Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.
However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.
This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.
On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.
Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.
Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.
Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.
This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.
This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.
Progress, but Far From Reaching Targets
Fast-forward to 2023.
Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.
In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.
Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.
The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.
Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).
In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.
Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.
As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:
- A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
- HCV antibody testing with reflex to PCR should be used as the screening test.
- Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
- Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.
Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.
Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article appeared on Medscape.com.
Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.
Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.
The Sofosbuvir Revolution Begins
The Liver Meeting held in 2013 changed everything.
Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.
However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.
This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.
On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.
Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.
Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.
Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.
This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.
This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.
Progress, but Far From Reaching Targets
Fast-forward to 2023.
Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.
In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.
Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.
The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.
Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).
In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.
Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.
As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:
- A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
- HCV antibody testing with reflex to PCR should be used as the screening test.
- Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
- Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.
Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.
Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article appeared on Medscape.com.