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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Novel combo drug shows promise as first-line Parkinson’s disease treatment
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
CO2 laser excision therapy for hidradenitis suppurativa shows no keloid risk
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT SOCS 2022
TAVI device shows less deterioration than surgery 5 years out
Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.
For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.
“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.
In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).
As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.
The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.
In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.
More than 4,000 patients evaluated at 5 years
In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.
SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.
When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.
There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).
In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
SVD linked to doubling of mortality
SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).
The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.
Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.
“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.
This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.
Several experts agreed that this is important new information.
“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.
Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.
Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.
“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”
Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.
Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.
For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.
“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.
In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).
As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.
The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.
In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.
More than 4,000 patients evaluated at 5 years
In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.
SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.
When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.
There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).
In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
SVD linked to doubling of mortality
SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).
The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.
Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.
“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.
This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.
Several experts agreed that this is important new information.
“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.
Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.
Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.
“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”
Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.
Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.
For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.
“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.
In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).
As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.
The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.
In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.
More than 4,000 patients evaluated at 5 years
In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.
SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.
When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.
There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).
In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
SVD linked to doubling of mortality
SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).
The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.
Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.
“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.
This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.
Several experts agreed that this is important new information.
“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.
Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.
Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.
“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”
Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.
FROM ACC 2022
Antibody reduces amyloid, induces symptom decline
SEATTLE – The researchers identified two plasma biomarkers that correlate well with established amyloid PET standard uptake value ratio (SUVr) changes, potentially paving the way for monitoring lecanemab treatment effects. The researchers also found evidence that the plasma biomarker could be used to allow dose frequency reduction after initial reduction in amyloid plaques.
Lecanemab preferably targets aggregated species of amyloid called protofibrils, which is unique among anti-amyloid antibodies, and these are also among the most toxic manifestations of amyloid, according to Chad Swanson, PhD, who presented the study at the 2022 annual meeting of the American Academy of Neurology.
Are amyloid plaques a key driver of Alzheimer’s disease?
The study could help answer the question of whether amyloid plaques drive the cognitive decline seen in Alzheimer’s disease, in part because the antibody is so effective at what it was designed to do, according to Fernando Testai, MD, PhD, who comoderated the session where the study was presented. “The effect on amyloid content that they measured was persistent over a number of months. Cognition may follow along, so more studies have to be done, but the medication seems to be quite effective doing what it’s supposed to do. If it has something to do with disease, these treatments actually should give us the answer, because the effect on amyloid is pretty significant. After so many years of thinking amyloid probably has nothing to do (with Alzheimer’s symptoms, these results suggest) it may have something to do with the disease,” Dr. Testai said in an interview. He is a professor of neurology at the University of Illinois at Chicago.
Dr. Swanson is confident that amyloid plaques are a key driver of disease. “I’d say a number of companies now with anti-amyloid agents have shown that targeting amyloid can produce some slowing of clinical decline, as well as a robust reduction in amyloid, supporting this idea that that amyloid is meaningful. And it’s very clear that amyloid [deposition] tends to trigger tau pathology,” said Dr. Swanson in an interview. He is executive director of the neurology business group at Eisai Pharmaceuticals, which is developing the anti-amyloid antibody, called lecanemab.
Searching for the best dose and dose frequency
Dr. Swanson noted that Eisai has already conducted a large phase 2b study which informed the current phase 3 ClarityAD study design. The phase 2b study utilized a Bayesian adaptive design, which allocated more patients in a fully blinded way to doses that had the most potential for slowing clinical decline. “The intent was to maximize the efficiency of the design so that more subjects would go to a dose that looks like it could be the best dose according to the Bayesian algorithm,” said Dr. Swanson.
The study also included a gap period that followed the randomized phase of the trial, where subjects were not being dosed with the antibody from 9 to 59 months (mean, 2 years), before reinitiation at the start of the open-label extension phase. “[That] allowed us to answer some really important questions about what happens when you remove lecanemab after reducing amyloid, and then what happens when you reintroduce lecanemab in the open-label extension,” said Dr. Swanson.
The researchers found that amyloid reaccumulated during the treatment gap, and soluble biomarkers were potentially the most sensitive to the change. “Taking all of this information together with clinical data that suggest potential disease-modifying effects, it suggests that we need to continue to treat these individuals, but we may be able to treat with a less-frequent dosing interval once amyloid is removed from the brain. It’s a biweekly infusion. Following 18 months of treatment, we may be able to go in once every month or once every 3 months to maintain low levels of amyloid. We’re going to be testing that soon in the current phase 2 open-label extension,” said Dr. Swanson.
The study included 856 patients who were randomized to biweekly placebo or lecanemab 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, or 10 mg/kg biweekly. The primary endpoint was the Alzheimer’s disease composite score at 12 months; secondary endpoints included ADCOMS and various biomarker levels at 18 months.
At 18 months, the 10-mg/kg biweekly group had an adjusted mean change from placebo in brain amyloid of –0.31 SUVr units, with more than 80% of the subjects converting from amyloid positive to amyloid negative by visual read. Most subjects remained amyloid negative at open-label extension baseline following the gap period despite a slow reaccumulation of amyloid plaque in the treated group. Out to 18 months in the core study, the same group had a 30% reduction in cognitive decline, compared with placebo, as measured by ADCOMS (P < .05).
There was a correlation between PET SUVr, clinical outcomes, and the Abeta42/40 ratio and plasma p-tau181. During the gap period, treatment discontinuation was associated with changes in the plasma biomarkers that echoed amyloid re-accumulation and clinical decline. Change from baseline in both plasma biomarkers were associated with a change from baseline in PET SUVr at 18 months.
Amyloid-related imaging abnormalities related to brain edema or sulcal effusion (ARIA-E) occurred in 9.9% of patients during the randomized phase of the trial, and 7.8% during the open-label extension phase. About 2% were symptomatic in both the randomization and open-label extension phases. The majority of ARIA-E cases appeared within 3 months of treatment initiation, and generally resolved in 4-16 weeks. 80% were mild to moderate by radiography.
Dr. Swanson is an employee of Eisai Pharmaceuticals, which sponsored the study. Dr. Testai has no relevant financial disclosures.
SEATTLE – The researchers identified two plasma biomarkers that correlate well with established amyloid PET standard uptake value ratio (SUVr) changes, potentially paving the way for monitoring lecanemab treatment effects. The researchers also found evidence that the plasma biomarker could be used to allow dose frequency reduction after initial reduction in amyloid plaques.
Lecanemab preferably targets aggregated species of amyloid called protofibrils, which is unique among anti-amyloid antibodies, and these are also among the most toxic manifestations of amyloid, according to Chad Swanson, PhD, who presented the study at the 2022 annual meeting of the American Academy of Neurology.
Are amyloid plaques a key driver of Alzheimer’s disease?
The study could help answer the question of whether amyloid plaques drive the cognitive decline seen in Alzheimer’s disease, in part because the antibody is so effective at what it was designed to do, according to Fernando Testai, MD, PhD, who comoderated the session where the study was presented. “The effect on amyloid content that they measured was persistent over a number of months. Cognition may follow along, so more studies have to be done, but the medication seems to be quite effective doing what it’s supposed to do. If it has something to do with disease, these treatments actually should give us the answer, because the effect on amyloid is pretty significant. After so many years of thinking amyloid probably has nothing to do (with Alzheimer’s symptoms, these results suggest) it may have something to do with the disease,” Dr. Testai said in an interview. He is a professor of neurology at the University of Illinois at Chicago.
Dr. Swanson is confident that amyloid plaques are a key driver of disease. “I’d say a number of companies now with anti-amyloid agents have shown that targeting amyloid can produce some slowing of clinical decline, as well as a robust reduction in amyloid, supporting this idea that that amyloid is meaningful. And it’s very clear that amyloid [deposition] tends to trigger tau pathology,” said Dr. Swanson in an interview. He is executive director of the neurology business group at Eisai Pharmaceuticals, which is developing the anti-amyloid antibody, called lecanemab.
Searching for the best dose and dose frequency
Dr. Swanson noted that Eisai has already conducted a large phase 2b study which informed the current phase 3 ClarityAD study design. The phase 2b study utilized a Bayesian adaptive design, which allocated more patients in a fully blinded way to doses that had the most potential for slowing clinical decline. “The intent was to maximize the efficiency of the design so that more subjects would go to a dose that looks like it could be the best dose according to the Bayesian algorithm,” said Dr. Swanson.
The study also included a gap period that followed the randomized phase of the trial, where subjects were not being dosed with the antibody from 9 to 59 months (mean, 2 years), before reinitiation at the start of the open-label extension phase. “[That] allowed us to answer some really important questions about what happens when you remove lecanemab after reducing amyloid, and then what happens when you reintroduce lecanemab in the open-label extension,” said Dr. Swanson.
The researchers found that amyloid reaccumulated during the treatment gap, and soluble biomarkers were potentially the most sensitive to the change. “Taking all of this information together with clinical data that suggest potential disease-modifying effects, it suggests that we need to continue to treat these individuals, but we may be able to treat with a less-frequent dosing interval once amyloid is removed from the brain. It’s a biweekly infusion. Following 18 months of treatment, we may be able to go in once every month or once every 3 months to maintain low levels of amyloid. We’re going to be testing that soon in the current phase 2 open-label extension,” said Dr. Swanson.
The study included 856 patients who were randomized to biweekly placebo or lecanemab 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, or 10 mg/kg biweekly. The primary endpoint was the Alzheimer’s disease composite score at 12 months; secondary endpoints included ADCOMS and various biomarker levels at 18 months.
At 18 months, the 10-mg/kg biweekly group had an adjusted mean change from placebo in brain amyloid of –0.31 SUVr units, with more than 80% of the subjects converting from amyloid positive to amyloid negative by visual read. Most subjects remained amyloid negative at open-label extension baseline following the gap period despite a slow reaccumulation of amyloid plaque in the treated group. Out to 18 months in the core study, the same group had a 30% reduction in cognitive decline, compared with placebo, as measured by ADCOMS (P < .05).
There was a correlation between PET SUVr, clinical outcomes, and the Abeta42/40 ratio and plasma p-tau181. During the gap period, treatment discontinuation was associated with changes in the plasma biomarkers that echoed amyloid re-accumulation and clinical decline. Change from baseline in both plasma biomarkers were associated with a change from baseline in PET SUVr at 18 months.
Amyloid-related imaging abnormalities related to brain edema or sulcal effusion (ARIA-E) occurred in 9.9% of patients during the randomized phase of the trial, and 7.8% during the open-label extension phase. About 2% were symptomatic in both the randomization and open-label extension phases. The majority of ARIA-E cases appeared within 3 months of treatment initiation, and generally resolved in 4-16 weeks. 80% were mild to moderate by radiography.
Dr. Swanson is an employee of Eisai Pharmaceuticals, which sponsored the study. Dr. Testai has no relevant financial disclosures.
SEATTLE – The researchers identified two plasma biomarkers that correlate well with established amyloid PET standard uptake value ratio (SUVr) changes, potentially paving the way for monitoring lecanemab treatment effects. The researchers also found evidence that the plasma biomarker could be used to allow dose frequency reduction after initial reduction in amyloid plaques.
Lecanemab preferably targets aggregated species of amyloid called protofibrils, which is unique among anti-amyloid antibodies, and these are also among the most toxic manifestations of amyloid, according to Chad Swanson, PhD, who presented the study at the 2022 annual meeting of the American Academy of Neurology.
Are amyloid plaques a key driver of Alzheimer’s disease?
The study could help answer the question of whether amyloid plaques drive the cognitive decline seen in Alzheimer’s disease, in part because the antibody is so effective at what it was designed to do, according to Fernando Testai, MD, PhD, who comoderated the session where the study was presented. “The effect on amyloid content that they measured was persistent over a number of months. Cognition may follow along, so more studies have to be done, but the medication seems to be quite effective doing what it’s supposed to do. If it has something to do with disease, these treatments actually should give us the answer, because the effect on amyloid is pretty significant. After so many years of thinking amyloid probably has nothing to do (with Alzheimer’s symptoms, these results suggest) it may have something to do with the disease,” Dr. Testai said in an interview. He is a professor of neurology at the University of Illinois at Chicago.
Dr. Swanson is confident that amyloid plaques are a key driver of disease. “I’d say a number of companies now with anti-amyloid agents have shown that targeting amyloid can produce some slowing of clinical decline, as well as a robust reduction in amyloid, supporting this idea that that amyloid is meaningful. And it’s very clear that amyloid [deposition] tends to trigger tau pathology,” said Dr. Swanson in an interview. He is executive director of the neurology business group at Eisai Pharmaceuticals, which is developing the anti-amyloid antibody, called lecanemab.
Searching for the best dose and dose frequency
Dr. Swanson noted that Eisai has already conducted a large phase 2b study which informed the current phase 3 ClarityAD study design. The phase 2b study utilized a Bayesian adaptive design, which allocated more patients in a fully blinded way to doses that had the most potential for slowing clinical decline. “The intent was to maximize the efficiency of the design so that more subjects would go to a dose that looks like it could be the best dose according to the Bayesian algorithm,” said Dr. Swanson.
The study also included a gap period that followed the randomized phase of the trial, where subjects were not being dosed with the antibody from 9 to 59 months (mean, 2 years), before reinitiation at the start of the open-label extension phase. “[That] allowed us to answer some really important questions about what happens when you remove lecanemab after reducing amyloid, and then what happens when you reintroduce lecanemab in the open-label extension,” said Dr. Swanson.
The researchers found that amyloid reaccumulated during the treatment gap, and soluble biomarkers were potentially the most sensitive to the change. “Taking all of this information together with clinical data that suggest potential disease-modifying effects, it suggests that we need to continue to treat these individuals, but we may be able to treat with a less-frequent dosing interval once amyloid is removed from the brain. It’s a biweekly infusion. Following 18 months of treatment, we may be able to go in once every month or once every 3 months to maintain low levels of amyloid. We’re going to be testing that soon in the current phase 2 open-label extension,” said Dr. Swanson.
The study included 856 patients who were randomized to biweekly placebo or lecanemab 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, or 10 mg/kg biweekly. The primary endpoint was the Alzheimer’s disease composite score at 12 months; secondary endpoints included ADCOMS and various biomarker levels at 18 months.
At 18 months, the 10-mg/kg biweekly group had an adjusted mean change from placebo in brain amyloid of –0.31 SUVr units, with more than 80% of the subjects converting from amyloid positive to amyloid negative by visual read. Most subjects remained amyloid negative at open-label extension baseline following the gap period despite a slow reaccumulation of amyloid plaque in the treated group. Out to 18 months in the core study, the same group had a 30% reduction in cognitive decline, compared with placebo, as measured by ADCOMS (P < .05).
There was a correlation between PET SUVr, clinical outcomes, and the Abeta42/40 ratio and plasma p-tau181. During the gap period, treatment discontinuation was associated with changes in the plasma biomarkers that echoed amyloid re-accumulation and clinical decline. Change from baseline in both plasma biomarkers were associated with a change from baseline in PET SUVr at 18 months.
Amyloid-related imaging abnormalities related to brain edema or sulcal effusion (ARIA-E) occurred in 9.9% of patients during the randomized phase of the trial, and 7.8% during the open-label extension phase. About 2% were symptomatic in both the randomization and open-label extension phases. The majority of ARIA-E cases appeared within 3 months of treatment initiation, and generally resolved in 4-16 weeks. 80% were mild to moderate by radiography.
Dr. Swanson is an employee of Eisai Pharmaceuticals, which sponsored the study. Dr. Testai has no relevant financial disclosures.
AT AAN 2022
Study: Disparities shrink with aggressive depression screening
The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.
In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.
Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.
“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
Methods for identifying depression
The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.
Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.
During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.
Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
Screening disparities narrowed for all groups studied
The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).
Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.
Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.
“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.
Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.
Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.
In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.
Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.
“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
Methods for identifying depression
The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.
Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.
During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.
Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
Screening disparities narrowed for all groups studied
The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).
Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.
Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.
“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.
Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.
Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.
In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.
Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.
“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
Methods for identifying depression
The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.
Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.
During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.
Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
Screening disparities narrowed for all groups studied
The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).
Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.
Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.
“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.
Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.
Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SGIM 2022
Renal denervation BP benefits remain at 3 years: SPYRAL HTN-ON
Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.
At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.
The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).
Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).
The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.
“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.
The results are specific to the Symplicity Spyral catheter, which is investigational in the United States and may not be generalizable to other renal denervation devices, he added.
“The fact you have been able to accomplish this really is quite a feat,” said discussant Martin Leon, MD, New York-Presbyterian/Columbia University Irving Medical Center. “I would argue that the results at 36 months are at least as important as the ones at 6 months.”
He observed that one of the promises of renal denervation, however, is that it would be able to reduce patients’ drug burden with fewer drugs and lesser doses.
“At least in this trial, there was very little effect in terms of significantly reducing the pharmacologic burden,” Dr. Leon said. “So, it would be difficult for me to be able to say to patients that receiving renal denervation will reduce the number of medications you would need to treat. In fact, it increased from two to three drugs over the course of follow-up.”
The objective of the trial was not to reduce medication burden but to get blood pressure (BP) controlled in patients with an average baseline office reading of 164.4/99.5 mm Hg, Dr. Mahfoud replied. “We have shown that office systolic blood pressure decreased by around 20 millimeters of mercury in combination with drugs, so it may be seen as an alternative to antihypertensive medication in patients who are in need of getting blood pressure control.”
Dr. Leon responded that the BP control differences are “very dramatic and certainly very important” but that the word adjunctive can be tricky. “I’m trying to understand if it’s the independent or isolated effect of the renal denervation or if it’s a sensitivity to the biological or physiologic milieux which enhances the efficacy of the adjunctive drugs, especially with the fact that over time, it looked like you had increasing effects at some distance from the initial index procedure.”
Dr. Mahfoud said that previous work has shown that renal denervation reduces plasma renin activity and aldosterone concentrations. “It’s not fully understood, but I guess there are synergistic effects of denervation in combination with drugs.”
Sham-controlled evidence
As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.
The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.
Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.
At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).
Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).
Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.
“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”
The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”
A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.
“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”
Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.
Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.
At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.
The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).
Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).
The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.
“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.
The results are specific to the Symplicity Spyral catheter, which is investigational in the United States and may not be generalizable to other renal denervation devices, he added.
“The fact you have been able to accomplish this really is quite a feat,” said discussant Martin Leon, MD, New York-Presbyterian/Columbia University Irving Medical Center. “I would argue that the results at 36 months are at least as important as the ones at 6 months.”
He observed that one of the promises of renal denervation, however, is that it would be able to reduce patients’ drug burden with fewer drugs and lesser doses.
“At least in this trial, there was very little effect in terms of significantly reducing the pharmacologic burden,” Dr. Leon said. “So, it would be difficult for me to be able to say to patients that receiving renal denervation will reduce the number of medications you would need to treat. In fact, it increased from two to three drugs over the course of follow-up.”
The objective of the trial was not to reduce medication burden but to get blood pressure (BP) controlled in patients with an average baseline office reading of 164.4/99.5 mm Hg, Dr. Mahfoud replied. “We have shown that office systolic blood pressure decreased by around 20 millimeters of mercury in combination with drugs, so it may be seen as an alternative to antihypertensive medication in patients who are in need of getting blood pressure control.”
Dr. Leon responded that the BP control differences are “very dramatic and certainly very important” but that the word adjunctive can be tricky. “I’m trying to understand if it’s the independent or isolated effect of the renal denervation or if it’s a sensitivity to the biological or physiologic milieux which enhances the efficacy of the adjunctive drugs, especially with the fact that over time, it looked like you had increasing effects at some distance from the initial index procedure.”
Dr. Mahfoud said that previous work has shown that renal denervation reduces plasma renin activity and aldosterone concentrations. “It’s not fully understood, but I guess there are synergistic effects of denervation in combination with drugs.”
Sham-controlled evidence
As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.
The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.
Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.
At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).
Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).
Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.
“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”
The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”
A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.
“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”
Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.
Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.
At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.
The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).
Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).
The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.
“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.
The results are specific to the Symplicity Spyral catheter, which is investigational in the United States and may not be generalizable to other renal denervation devices, he added.
“The fact you have been able to accomplish this really is quite a feat,” said discussant Martin Leon, MD, New York-Presbyterian/Columbia University Irving Medical Center. “I would argue that the results at 36 months are at least as important as the ones at 6 months.”
He observed that one of the promises of renal denervation, however, is that it would be able to reduce patients’ drug burden with fewer drugs and lesser doses.
“At least in this trial, there was very little effect in terms of significantly reducing the pharmacologic burden,” Dr. Leon said. “So, it would be difficult for me to be able to say to patients that receiving renal denervation will reduce the number of medications you would need to treat. In fact, it increased from two to three drugs over the course of follow-up.”
The objective of the trial was not to reduce medication burden but to get blood pressure (BP) controlled in patients with an average baseline office reading of 164.4/99.5 mm Hg, Dr. Mahfoud replied. “We have shown that office systolic blood pressure decreased by around 20 millimeters of mercury in combination with drugs, so it may be seen as an alternative to antihypertensive medication in patients who are in need of getting blood pressure control.”
Dr. Leon responded that the BP control differences are “very dramatic and certainly very important” but that the word adjunctive can be tricky. “I’m trying to understand if it’s the independent or isolated effect of the renal denervation or if it’s a sensitivity to the biological or physiologic milieux which enhances the efficacy of the adjunctive drugs, especially with the fact that over time, it looked like you had increasing effects at some distance from the initial index procedure.”
Dr. Mahfoud said that previous work has shown that renal denervation reduces plasma renin activity and aldosterone concentrations. “It’s not fully understood, but I guess there are synergistic effects of denervation in combination with drugs.”
Sham-controlled evidence
As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.
The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.
Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.
At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).
Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).
Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.
“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”
The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”
A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.
“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”
Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.
Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACC 2022
PLA testing brings nuance to the diagnosis of early-stage melanoma
BOSTON – Although
One such test, the Pigmented Lesional Assay (PLA) uses adhesive patches applied to lesions of concern at the bedside to extract RNA from the stratum corneum to help determine the risk for melanoma.
At the annual meeting of the American Academy of Dermatology, Caroline C. Kim, MD, director of melanoma and pigmented lesion clinics at Newton Wellesley Dermatology, Wellesley Hills, Mass., and Tufts Medical Center, Boston, spoke about the PLA, which uses genetic expression profiling to measure the expression level of specific genes that are associated with melanoma: PRAME (preferentially expressed antigen in melanoma) and LINC00518 (LINC). There are four possible results of the test: Aberrant expression of both LINC and PRAME (high risk); aberrant expression of a single gene (moderate risk); aberrant expression of neither gene (low risk); or inconclusive.
Validation data have shown a sensitivity of 91% and a specificity of 69% for the PLA, with a 99% negative predictive value; so a lesion that tested negative by PLA has a less than 1% chance of being melanoma. In addition, a study published in 2020 found that the addition of TERT (telomerase reverse transcriptase) mutation analyses increased the sensitivity of the PLA to 97%.
While the high negative predictive value is helpful to consider in clinical scenarios to rule-out melanoma for borderline lesions, one must consider the positive predictive value as well and how this may impact clinical care, Dr. Kim said. In a study examining outcomes of 381 lesions, 51 were PLA positive (single or double) and were biopsied, of which 19 (37%) revealed a melanoma diagnosis. In a large U.S. registry study of 3,418 lesions, 324 lesions that were PLA double positive were biopsied, with 18.7% revealing a melanoma diagnosis.
“No test is perfect, and this applies to PLA, even if you get a double-positive or double-negative test result,” Dr. Kim said. “You want to make sure that patients are aware of false positives and negatives. However, PLA could be an additional piece of data to inform your decision to proceed with biopsy on select borderline suspicious pigmented lesions. More studies are needed to better understand the approach to single- and double-positive PLA results.”
The PLA kit contains adhesive patches and supplies and a FedEx envelope for return to DermTech, the test’s manufacturer, for processing. The patches can be applied to lesions at least 4 mm in diameter; multiple kits are recommended for those greater than 16 mm in diameter. The test is not validated for lesions located on mucous membranes, palms, soles, nails, or on ulcerated or bleeding lesions, nor for those that have been previously biopsied. It is also not validated for use in pediatric patients or in those with skin types IV or higher. Results are returned in 2-3 days. If insurance does not cover the test, the cost to the patient is approximately $50 per lesion or a maximum of $150, according to Dr. Kim.
Use in clinical practice
In Dr. Kim’s clinical experience, the PLA can be considered for suspicious pigmented lesions on cosmetically sensitive areas and for suspicious lesions in areas difficult to biopsy or excise. For example, she discussed the case of a 72-year-old woman with a family history of melanoma, who presented to her clinic with a longstanding pigmented lesion on her right upper and lower eyelids that had previously been treated with laser. She had undergone multiple prior biopsies over 12 years, which caused mild to moderate atypical melanocytic proliferation. The PLA result was double negative for PRAME and LINC in her upper and lower eyelid, “which provided reassurance to the patient,” Dr. Kim said. The patient continues to be followed closely for any clinical changes.
Another patient, a 67-year-old woman, was referred to Dr. Kim from out of state for a teledermatology visit early in the COVID-19 pandemic. The patient had a lesion on her right calf that was hard, raised, and pink, did not resemble other lesions on her body, and had been present for a few weeks. “Her husband had recently passed away from brain cancer and she was very concerned about melanoma,” Dr. Kim recalled. “She lived alone, and the adult son was with her during the teledermatology call to assist. The patient asked about the PLA test, and given her difficulty going to a medical office at the time, we agreed to help her with this test.” The patient and her son arranged another teledermatology visit with Dr. Kim after receiving the kit in the mail from DermTech, and Dr. Kim coached them on how to properly administer the test. The results came back as PRAME negative and LINC positive. A biopsy with a local provider was recommended and the pathology results showed an inflamed seborrheic keratosis.
“This case exemplifies a false-positive result. We should be sure to make patients aware of this possibility,” Dr. Kim said.
Incorporating PLA into clinical practice requires certain workflow considerations, with paperwork to fill out in addition to performing the adhesive test, collection of insurance information, mailing the kit via FedEx, retrieving the results, and following up with the patient, said Dr. Kim. “For select borderline pigmented lesions, I discuss the rationale of the test with patients, the possibility of false-positive and false-negative results and the need to return for a biopsy when there is positive result. Clinical follow-up is recommended for negative results. There is also the possibility of charge to the patient if the test is not covered by their insurance.”
Skin biopsy still the gold standard
Despite the availability of the PLA as an assessment tool, Dr. Kim emphasized that skin biopsy remains the gold standard for diagnosing melanoma. “Future prospective randomized clinical trials are needed to examine the role of genetic expression profiling in staging and managing patients,” she said.
In 2019, she and her colleagues surveyed 42 pigmented lesion experts in the United States about why they ordered one of three molecular tests on the market or not and how results affected patient treatment. The proportion of clinicians who ordered the tests ranged from 21% to 29%. The top 2 reasons respondents chose for not ordering the PLA test specifically were: “Feel that further validation studies are necessary” (20%) and “do not feel it would be useful in my practice” (18%).
Results of a larger follow-up survey on usage patterns of PLA of both pigmented lesion experts and general clinicians on this topic are expected to be published shortly.
Dr. Kim reported having no disclosures related to her presentation.
BOSTON – Although
One such test, the Pigmented Lesional Assay (PLA) uses adhesive patches applied to lesions of concern at the bedside to extract RNA from the stratum corneum to help determine the risk for melanoma.
At the annual meeting of the American Academy of Dermatology, Caroline C. Kim, MD, director of melanoma and pigmented lesion clinics at Newton Wellesley Dermatology, Wellesley Hills, Mass., and Tufts Medical Center, Boston, spoke about the PLA, which uses genetic expression profiling to measure the expression level of specific genes that are associated with melanoma: PRAME (preferentially expressed antigen in melanoma) and LINC00518 (LINC). There are four possible results of the test: Aberrant expression of both LINC and PRAME (high risk); aberrant expression of a single gene (moderate risk); aberrant expression of neither gene (low risk); or inconclusive.
Validation data have shown a sensitivity of 91% and a specificity of 69% for the PLA, with a 99% negative predictive value; so a lesion that tested negative by PLA has a less than 1% chance of being melanoma. In addition, a study published in 2020 found that the addition of TERT (telomerase reverse transcriptase) mutation analyses increased the sensitivity of the PLA to 97%.
While the high negative predictive value is helpful to consider in clinical scenarios to rule-out melanoma for borderline lesions, one must consider the positive predictive value as well and how this may impact clinical care, Dr. Kim said. In a study examining outcomes of 381 lesions, 51 were PLA positive (single or double) and were biopsied, of which 19 (37%) revealed a melanoma diagnosis. In a large U.S. registry study of 3,418 lesions, 324 lesions that were PLA double positive were biopsied, with 18.7% revealing a melanoma diagnosis.
“No test is perfect, and this applies to PLA, even if you get a double-positive or double-negative test result,” Dr. Kim said. “You want to make sure that patients are aware of false positives and negatives. However, PLA could be an additional piece of data to inform your decision to proceed with biopsy on select borderline suspicious pigmented lesions. More studies are needed to better understand the approach to single- and double-positive PLA results.”
The PLA kit contains adhesive patches and supplies and a FedEx envelope for return to DermTech, the test’s manufacturer, for processing. The patches can be applied to lesions at least 4 mm in diameter; multiple kits are recommended for those greater than 16 mm in diameter. The test is not validated for lesions located on mucous membranes, palms, soles, nails, or on ulcerated or bleeding lesions, nor for those that have been previously biopsied. It is also not validated for use in pediatric patients or in those with skin types IV or higher. Results are returned in 2-3 days. If insurance does not cover the test, the cost to the patient is approximately $50 per lesion or a maximum of $150, according to Dr. Kim.
Use in clinical practice
In Dr. Kim’s clinical experience, the PLA can be considered for suspicious pigmented lesions on cosmetically sensitive areas and for suspicious lesions in areas difficult to biopsy or excise. For example, she discussed the case of a 72-year-old woman with a family history of melanoma, who presented to her clinic with a longstanding pigmented lesion on her right upper and lower eyelids that had previously been treated with laser. She had undergone multiple prior biopsies over 12 years, which caused mild to moderate atypical melanocytic proliferation. The PLA result was double negative for PRAME and LINC in her upper and lower eyelid, “which provided reassurance to the patient,” Dr. Kim said. The patient continues to be followed closely for any clinical changes.
Another patient, a 67-year-old woman, was referred to Dr. Kim from out of state for a teledermatology visit early in the COVID-19 pandemic. The patient had a lesion on her right calf that was hard, raised, and pink, did not resemble other lesions on her body, and had been present for a few weeks. “Her husband had recently passed away from brain cancer and she was very concerned about melanoma,” Dr. Kim recalled. “She lived alone, and the adult son was with her during the teledermatology call to assist. The patient asked about the PLA test, and given her difficulty going to a medical office at the time, we agreed to help her with this test.” The patient and her son arranged another teledermatology visit with Dr. Kim after receiving the kit in the mail from DermTech, and Dr. Kim coached them on how to properly administer the test. The results came back as PRAME negative and LINC positive. A biopsy with a local provider was recommended and the pathology results showed an inflamed seborrheic keratosis.
“This case exemplifies a false-positive result. We should be sure to make patients aware of this possibility,” Dr. Kim said.
Incorporating PLA into clinical practice requires certain workflow considerations, with paperwork to fill out in addition to performing the adhesive test, collection of insurance information, mailing the kit via FedEx, retrieving the results, and following up with the patient, said Dr. Kim. “For select borderline pigmented lesions, I discuss the rationale of the test with patients, the possibility of false-positive and false-negative results and the need to return for a biopsy when there is positive result. Clinical follow-up is recommended for negative results. There is also the possibility of charge to the patient if the test is not covered by their insurance.”
Skin biopsy still the gold standard
Despite the availability of the PLA as an assessment tool, Dr. Kim emphasized that skin biopsy remains the gold standard for diagnosing melanoma. “Future prospective randomized clinical trials are needed to examine the role of genetic expression profiling in staging and managing patients,” she said.
In 2019, she and her colleagues surveyed 42 pigmented lesion experts in the United States about why they ordered one of three molecular tests on the market or not and how results affected patient treatment. The proportion of clinicians who ordered the tests ranged from 21% to 29%. The top 2 reasons respondents chose for not ordering the PLA test specifically were: “Feel that further validation studies are necessary” (20%) and “do not feel it would be useful in my practice” (18%).
Results of a larger follow-up survey on usage patterns of PLA of both pigmented lesion experts and general clinicians on this topic are expected to be published shortly.
Dr. Kim reported having no disclosures related to her presentation.
BOSTON – Although
One such test, the Pigmented Lesional Assay (PLA) uses adhesive patches applied to lesions of concern at the bedside to extract RNA from the stratum corneum to help determine the risk for melanoma.
At the annual meeting of the American Academy of Dermatology, Caroline C. Kim, MD, director of melanoma and pigmented lesion clinics at Newton Wellesley Dermatology, Wellesley Hills, Mass., and Tufts Medical Center, Boston, spoke about the PLA, which uses genetic expression profiling to measure the expression level of specific genes that are associated with melanoma: PRAME (preferentially expressed antigen in melanoma) and LINC00518 (LINC). There are four possible results of the test: Aberrant expression of both LINC and PRAME (high risk); aberrant expression of a single gene (moderate risk); aberrant expression of neither gene (low risk); or inconclusive.
Validation data have shown a sensitivity of 91% and a specificity of 69% for the PLA, with a 99% negative predictive value; so a lesion that tested negative by PLA has a less than 1% chance of being melanoma. In addition, a study published in 2020 found that the addition of TERT (telomerase reverse transcriptase) mutation analyses increased the sensitivity of the PLA to 97%.
While the high negative predictive value is helpful to consider in clinical scenarios to rule-out melanoma for borderline lesions, one must consider the positive predictive value as well and how this may impact clinical care, Dr. Kim said. In a study examining outcomes of 381 lesions, 51 were PLA positive (single or double) and were biopsied, of which 19 (37%) revealed a melanoma diagnosis. In a large U.S. registry study of 3,418 lesions, 324 lesions that were PLA double positive were biopsied, with 18.7% revealing a melanoma diagnosis.
“No test is perfect, and this applies to PLA, even if you get a double-positive or double-negative test result,” Dr. Kim said. “You want to make sure that patients are aware of false positives and negatives. However, PLA could be an additional piece of data to inform your decision to proceed with biopsy on select borderline suspicious pigmented lesions. More studies are needed to better understand the approach to single- and double-positive PLA results.”
The PLA kit contains adhesive patches and supplies and a FedEx envelope for return to DermTech, the test’s manufacturer, for processing. The patches can be applied to lesions at least 4 mm in diameter; multiple kits are recommended for those greater than 16 mm in diameter. The test is not validated for lesions located on mucous membranes, palms, soles, nails, or on ulcerated or bleeding lesions, nor for those that have been previously biopsied. It is also not validated for use in pediatric patients or in those with skin types IV or higher. Results are returned in 2-3 days. If insurance does not cover the test, the cost to the patient is approximately $50 per lesion or a maximum of $150, according to Dr. Kim.
Use in clinical practice
In Dr. Kim’s clinical experience, the PLA can be considered for suspicious pigmented lesions on cosmetically sensitive areas and for suspicious lesions in areas difficult to biopsy or excise. For example, she discussed the case of a 72-year-old woman with a family history of melanoma, who presented to her clinic with a longstanding pigmented lesion on her right upper and lower eyelids that had previously been treated with laser. She had undergone multiple prior biopsies over 12 years, which caused mild to moderate atypical melanocytic proliferation. The PLA result was double negative for PRAME and LINC in her upper and lower eyelid, “which provided reassurance to the patient,” Dr. Kim said. The patient continues to be followed closely for any clinical changes.
Another patient, a 67-year-old woman, was referred to Dr. Kim from out of state for a teledermatology visit early in the COVID-19 pandemic. The patient had a lesion on her right calf that was hard, raised, and pink, did not resemble other lesions on her body, and had been present for a few weeks. “Her husband had recently passed away from brain cancer and she was very concerned about melanoma,” Dr. Kim recalled. “She lived alone, and the adult son was with her during the teledermatology call to assist. The patient asked about the PLA test, and given her difficulty going to a medical office at the time, we agreed to help her with this test.” The patient and her son arranged another teledermatology visit with Dr. Kim after receiving the kit in the mail from DermTech, and Dr. Kim coached them on how to properly administer the test. The results came back as PRAME negative and LINC positive. A biopsy with a local provider was recommended and the pathology results showed an inflamed seborrheic keratosis.
“This case exemplifies a false-positive result. We should be sure to make patients aware of this possibility,” Dr. Kim said.
Incorporating PLA into clinical practice requires certain workflow considerations, with paperwork to fill out in addition to performing the adhesive test, collection of insurance information, mailing the kit via FedEx, retrieving the results, and following up with the patient, said Dr. Kim. “For select borderline pigmented lesions, I discuss the rationale of the test with patients, the possibility of false-positive and false-negative results and the need to return for a biopsy when there is positive result. Clinical follow-up is recommended for negative results. There is also the possibility of charge to the patient if the test is not covered by their insurance.”
Skin biopsy still the gold standard
Despite the availability of the PLA as an assessment tool, Dr. Kim emphasized that skin biopsy remains the gold standard for diagnosing melanoma. “Future prospective randomized clinical trials are needed to examine the role of genetic expression profiling in staging and managing patients,” she said.
In 2019, she and her colleagues surveyed 42 pigmented lesion experts in the United States about why they ordered one of three molecular tests on the market or not and how results affected patient treatment. The proportion of clinicians who ordered the tests ranged from 21% to 29%. The top 2 reasons respondents chose for not ordering the PLA test specifically were: “Feel that further validation studies are necessary” (20%) and “do not feel it would be useful in my practice” (18%).
Results of a larger follow-up survey on usage patterns of PLA of both pigmented lesion experts and general clinicians on this topic are expected to be published shortly.
Dr. Kim reported having no disclosures related to her presentation.
AT AAD 22
Neighborhood-level data sheds new light on racial and ethnic diversity in MS
SEATTLE – These populations often have more severe disease, likely driven by socioeconomic factors and health care access, according to a new study that examined neighborhood-level data and disease severity in the United States.
“It has previously been thought that MS is less common among non-European Caucasian White populations, driven partly by the well-known association of incidence with latitude. It is abundantly clear at this point that this idea is not true,” said Christopher Orlando, MD, during a presentation at the 2022 annual meeting of the American Academy of Neurology.
He noted that several U.S. studies with large sample sizes have shown greater disease severity and a higher disability burden among Hispanic and Black patients. “Black patients in particular appear to have a higher incidence of disease and a greater proportion of progressive disease phenotypes,” said Dr. Orlando.
Race and ethnicity are unlikely explanations for this disparity, according to Dr. Orlando. “While much remains to be discovered of the genetic underpinnings of MS, what we do know does not support the idea that minorities would have a predilection to more severe disease. For example, the well-known high-risk allele HLA DRB1*1501 appears to have a lower frequency in African populations, compared with European [populations].”
Instead, evidence suggests that interrelated social causes include access to resources, environmental exposures, and psychosocial stress. “These affect health via a number of pathways including direct physical injury, allostatic load, and access to health care,” said Dr. Orlando.
Probing racial and ethnic disparities
Previous studies that corrected for social determinants of health such as socioeconomic and insurance status reduce the association between MS disability and race, but they do not completely explain it.
To get a better understanding of the impacts of these factors, researchers have used neighborhood-level data combined with information on socioeconomic status and social deprivation to identify associations with MS severity.
At the conference, Dr. Orlando presented a new study that is the first to use this methodology in the United States, and it is the first to apply it to the study of racial and ethnic disparities in MS.
The study confirmed more severe disability in Hispanic and Black patients than in White patients. Clinical factors associated with more severe disease were similar across the three groups, with some small differences among individual traits. “More stark differences appeared when we compared social determinants of health. Hispanic patients were less likely to speak English as a primary language or to complete 12 years of education. Black patients were less likely to live in a rural county and more likely to be unemployed. One particularly stark difference was in the number of unemployed specifically due to their MS, with only 1 White patient [1.1%], 7 Hispanic patients [7.8%] and 27 Black patients [31.0%],” said Dr. Orlando.
The researchers found that Black and Hispanic patients tend to live in more vulnerable neighborhoods than White patients. The researchers found no significant association between social vulnerability index (SVI) values and MS severity, though there was an association in a separate analysis that only included White patients. The SVI uses 15 measures taken from the U.S. Census to identify communities that might require additional support during natural disasters.
“It would appear that the sheer complexity both in variety and magnitude of the social determinants of health are such that by far the stronger association is with race and ethnicity, which are surrogates for any number of social determinants and societal inequities,” said Dr. Orlando.
What drives the inequity?
Dr. Orlando acknowledged that some might wonder if these results indicate a true biologically intrinsic factor such as genetic predisposition. “I want to warn against that kind of thinking in the strongest possible terms. It is implausible on several levels. It’s not biologically plausible based on our understanding that race and ethnicity are not genetic constructs. And it’s also not numerically plausible based on these data,” said Dr. Orlando.
While some of the drivers of this inequity have been partially examined, many have not been studied. “As long as this is the case, our ability to fulfill our roles as physicians will be limited in several important ways. Our ability to assess our patients’ individual risk will be missing key information, which will limit the efficacy of shared decision-making, which of course is the cornerstone of MS treatment. In addition, we will continue to struggle to include minority patients in our research studies, and the very design and results of those studies may be misguided, as we will either fail to include these populations, or we will fail to adjust for important confounders,” he said.
New answers, new questions
The neighborhood-level data examined by Dr. Orlando’s group “brings extra information in terms of the negative impact of social determinants of health. The disparity seen in neighborhood living is quite striking,” said Lilyana Amezcua, MD, who served as a discussant for Dr. Orlando’s presentation. The study reinforces findings of her own group in Hispanic and Latinx individuals with MS. Some comorbidities are more common among these groups, which is exacerbated by poor health access.
“We have noted that almost 30% of them also have this comorbidity of hypertension, but what is also observed is that only 7% of them are aware [that they have hypertension],” said Dr. Amezcua, who is an associate professor of neurology at the University of Southern California, Los Angeles.
The findings should prompt further research to understand the impact of systemic racism and neighborhood factors, such as disinvestment in the public and private sectors, underresourced hospitals and clinics, and negative infrastructure. “We need to start discussing the (patient’s) environment so we can better understand the community resources they may have available, as well as create innovative transitional care services. We need to also recognize and accept that structural racism and imbalanced distribution of resources and neighborhoods does restrict educational and economic opportunities, as well as health care access and the safety of these marginalized communities,” said Dr. Amezcua.
Dr. Amezcua has consulted for, received speaking fees from, or served on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono. She has received research support from the Bristol-Myers Squibb Foundation and Biogen Idec. Dr. Orlando has no relevant financial disclosures.
SEATTLE – These populations often have more severe disease, likely driven by socioeconomic factors and health care access, according to a new study that examined neighborhood-level data and disease severity in the United States.
“It has previously been thought that MS is less common among non-European Caucasian White populations, driven partly by the well-known association of incidence with latitude. It is abundantly clear at this point that this idea is not true,” said Christopher Orlando, MD, during a presentation at the 2022 annual meeting of the American Academy of Neurology.
He noted that several U.S. studies with large sample sizes have shown greater disease severity and a higher disability burden among Hispanic and Black patients. “Black patients in particular appear to have a higher incidence of disease and a greater proportion of progressive disease phenotypes,” said Dr. Orlando.
Race and ethnicity are unlikely explanations for this disparity, according to Dr. Orlando. “While much remains to be discovered of the genetic underpinnings of MS, what we do know does not support the idea that minorities would have a predilection to more severe disease. For example, the well-known high-risk allele HLA DRB1*1501 appears to have a lower frequency in African populations, compared with European [populations].”
Instead, evidence suggests that interrelated social causes include access to resources, environmental exposures, and psychosocial stress. “These affect health via a number of pathways including direct physical injury, allostatic load, and access to health care,” said Dr. Orlando.
Probing racial and ethnic disparities
Previous studies that corrected for social determinants of health such as socioeconomic and insurance status reduce the association between MS disability and race, but they do not completely explain it.
To get a better understanding of the impacts of these factors, researchers have used neighborhood-level data combined with information on socioeconomic status and social deprivation to identify associations with MS severity.
At the conference, Dr. Orlando presented a new study that is the first to use this methodology in the United States, and it is the first to apply it to the study of racial and ethnic disparities in MS.
The study confirmed more severe disability in Hispanic and Black patients than in White patients. Clinical factors associated with more severe disease were similar across the three groups, with some small differences among individual traits. “More stark differences appeared when we compared social determinants of health. Hispanic patients were less likely to speak English as a primary language or to complete 12 years of education. Black patients were less likely to live in a rural county and more likely to be unemployed. One particularly stark difference was in the number of unemployed specifically due to their MS, with only 1 White patient [1.1%], 7 Hispanic patients [7.8%] and 27 Black patients [31.0%],” said Dr. Orlando.
The researchers found that Black and Hispanic patients tend to live in more vulnerable neighborhoods than White patients. The researchers found no significant association between social vulnerability index (SVI) values and MS severity, though there was an association in a separate analysis that only included White patients. The SVI uses 15 measures taken from the U.S. Census to identify communities that might require additional support during natural disasters.
“It would appear that the sheer complexity both in variety and magnitude of the social determinants of health are such that by far the stronger association is with race and ethnicity, which are surrogates for any number of social determinants and societal inequities,” said Dr. Orlando.
What drives the inequity?
Dr. Orlando acknowledged that some might wonder if these results indicate a true biologically intrinsic factor such as genetic predisposition. “I want to warn against that kind of thinking in the strongest possible terms. It is implausible on several levels. It’s not biologically plausible based on our understanding that race and ethnicity are not genetic constructs. And it’s also not numerically plausible based on these data,” said Dr. Orlando.
While some of the drivers of this inequity have been partially examined, many have not been studied. “As long as this is the case, our ability to fulfill our roles as physicians will be limited in several important ways. Our ability to assess our patients’ individual risk will be missing key information, which will limit the efficacy of shared decision-making, which of course is the cornerstone of MS treatment. In addition, we will continue to struggle to include minority patients in our research studies, and the very design and results of those studies may be misguided, as we will either fail to include these populations, or we will fail to adjust for important confounders,” he said.
New answers, new questions
The neighborhood-level data examined by Dr. Orlando’s group “brings extra information in terms of the negative impact of social determinants of health. The disparity seen in neighborhood living is quite striking,” said Lilyana Amezcua, MD, who served as a discussant for Dr. Orlando’s presentation. The study reinforces findings of her own group in Hispanic and Latinx individuals with MS. Some comorbidities are more common among these groups, which is exacerbated by poor health access.
“We have noted that almost 30% of them also have this comorbidity of hypertension, but what is also observed is that only 7% of them are aware [that they have hypertension],” said Dr. Amezcua, who is an associate professor of neurology at the University of Southern California, Los Angeles.
The findings should prompt further research to understand the impact of systemic racism and neighborhood factors, such as disinvestment in the public and private sectors, underresourced hospitals and clinics, and negative infrastructure. “We need to start discussing the (patient’s) environment so we can better understand the community resources they may have available, as well as create innovative transitional care services. We need to also recognize and accept that structural racism and imbalanced distribution of resources and neighborhoods does restrict educational and economic opportunities, as well as health care access and the safety of these marginalized communities,” said Dr. Amezcua.
Dr. Amezcua has consulted for, received speaking fees from, or served on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono. She has received research support from the Bristol-Myers Squibb Foundation and Biogen Idec. Dr. Orlando has no relevant financial disclosures.
SEATTLE – These populations often have more severe disease, likely driven by socioeconomic factors and health care access, according to a new study that examined neighborhood-level data and disease severity in the United States.
“It has previously been thought that MS is less common among non-European Caucasian White populations, driven partly by the well-known association of incidence with latitude. It is abundantly clear at this point that this idea is not true,” said Christopher Orlando, MD, during a presentation at the 2022 annual meeting of the American Academy of Neurology.
He noted that several U.S. studies with large sample sizes have shown greater disease severity and a higher disability burden among Hispanic and Black patients. “Black patients in particular appear to have a higher incidence of disease and a greater proportion of progressive disease phenotypes,” said Dr. Orlando.
Race and ethnicity are unlikely explanations for this disparity, according to Dr. Orlando. “While much remains to be discovered of the genetic underpinnings of MS, what we do know does not support the idea that minorities would have a predilection to more severe disease. For example, the well-known high-risk allele HLA DRB1*1501 appears to have a lower frequency in African populations, compared with European [populations].”
Instead, evidence suggests that interrelated social causes include access to resources, environmental exposures, and psychosocial stress. “These affect health via a number of pathways including direct physical injury, allostatic load, and access to health care,” said Dr. Orlando.
Probing racial and ethnic disparities
Previous studies that corrected for social determinants of health such as socioeconomic and insurance status reduce the association between MS disability and race, but they do not completely explain it.
To get a better understanding of the impacts of these factors, researchers have used neighborhood-level data combined with information on socioeconomic status and social deprivation to identify associations with MS severity.
At the conference, Dr. Orlando presented a new study that is the first to use this methodology in the United States, and it is the first to apply it to the study of racial and ethnic disparities in MS.
The study confirmed more severe disability in Hispanic and Black patients than in White patients. Clinical factors associated with more severe disease were similar across the three groups, with some small differences among individual traits. “More stark differences appeared when we compared social determinants of health. Hispanic patients were less likely to speak English as a primary language or to complete 12 years of education. Black patients were less likely to live in a rural county and more likely to be unemployed. One particularly stark difference was in the number of unemployed specifically due to their MS, with only 1 White patient [1.1%], 7 Hispanic patients [7.8%] and 27 Black patients [31.0%],” said Dr. Orlando.
The researchers found that Black and Hispanic patients tend to live in more vulnerable neighborhoods than White patients. The researchers found no significant association between social vulnerability index (SVI) values and MS severity, though there was an association in a separate analysis that only included White patients. The SVI uses 15 measures taken from the U.S. Census to identify communities that might require additional support during natural disasters.
“It would appear that the sheer complexity both in variety and magnitude of the social determinants of health are such that by far the stronger association is with race and ethnicity, which are surrogates for any number of social determinants and societal inequities,” said Dr. Orlando.
What drives the inequity?
Dr. Orlando acknowledged that some might wonder if these results indicate a true biologically intrinsic factor such as genetic predisposition. “I want to warn against that kind of thinking in the strongest possible terms. It is implausible on several levels. It’s not biologically plausible based on our understanding that race and ethnicity are not genetic constructs. And it’s also not numerically plausible based on these data,” said Dr. Orlando.
While some of the drivers of this inequity have been partially examined, many have not been studied. “As long as this is the case, our ability to fulfill our roles as physicians will be limited in several important ways. Our ability to assess our patients’ individual risk will be missing key information, which will limit the efficacy of shared decision-making, which of course is the cornerstone of MS treatment. In addition, we will continue to struggle to include minority patients in our research studies, and the very design and results of those studies may be misguided, as we will either fail to include these populations, or we will fail to adjust for important confounders,” he said.
New answers, new questions
The neighborhood-level data examined by Dr. Orlando’s group “brings extra information in terms of the negative impact of social determinants of health. The disparity seen in neighborhood living is quite striking,” said Lilyana Amezcua, MD, who served as a discussant for Dr. Orlando’s presentation. The study reinforces findings of her own group in Hispanic and Latinx individuals with MS. Some comorbidities are more common among these groups, which is exacerbated by poor health access.
“We have noted that almost 30% of them also have this comorbidity of hypertension, but what is also observed is that only 7% of them are aware [that they have hypertension],” said Dr. Amezcua, who is an associate professor of neurology at the University of Southern California, Los Angeles.
The findings should prompt further research to understand the impact of systemic racism and neighborhood factors, such as disinvestment in the public and private sectors, underresourced hospitals and clinics, and negative infrastructure. “We need to start discussing the (patient’s) environment so we can better understand the community resources they may have available, as well as create innovative transitional care services. We need to also recognize and accept that structural racism and imbalanced distribution of resources and neighborhoods does restrict educational and economic opportunities, as well as health care access and the safety of these marginalized communities,” said Dr. Amezcua.
Dr. Amezcua has consulted for, received speaking fees from, or served on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono. She has received research support from the Bristol-Myers Squibb Foundation and Biogen Idec. Dr. Orlando has no relevant financial disclosures.
AT AAN 2022
Study finds discrepancies in biopsy decisions, diagnoses based on skin type
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rapper sings about living with sickle cell disease
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.