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AI tool predicts certain GI cancers years in advance
TOPLINE:
and is more accurate than other tools, a large study suggests.
METHODOLOGY:
- Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
- They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
- K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.
TAKEAWAY:
- With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
- Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
- K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
- Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.
IN PRACTICE:
Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.
SOURCE:
The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.
LIMITATIONS:
K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.
DISCLOSURES:
Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.
A version of this article first appeared on Medscape.com.
TOPLINE:
and is more accurate than other tools, a large study suggests.
METHODOLOGY:
- Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
- They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
- K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.
TAKEAWAY:
- With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
- Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
- K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
- Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.
IN PRACTICE:
Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.
SOURCE:
The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.
LIMITATIONS:
K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.
DISCLOSURES:
Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.
A version of this article first appeared on Medscape.com.
TOPLINE:
and is more accurate than other tools, a large study suggests.
METHODOLOGY:
- Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
- They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
- K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.
TAKEAWAY:
- With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
- Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
- K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
- Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.
IN PRACTICE:
Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.
SOURCE:
The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.
LIMITATIONS:
K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.
DISCLOSURES:
Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.
A version of this article first appeared on Medscape.com.
FROM GASTROENTEROLOGY
Probiotics improve nonmotor symptoms of Parkinson’s
COPENHAGEN – results of a new randomized trial show.
Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, PhD, department of neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience.
Dr. Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders.
“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Dr. Leta told attendees of the congress.
A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including proinflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”
However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited ... to the treatment of constipation,” she explained.
The team therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.
The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.
A total of 74 patients were randomly assigned to the two study arms. The two groups were well matched for sociodemographics, Parkinson’s disease, and constipation-related characteristics, Dr. Leta reported, and only 3 patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events.”
Increase in healthy bacteria
The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.
The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Dr. Leta said.
This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”
The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the postintervention assessment (P < .027).
There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the postintervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).
This, Dr. Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”
No such significant improvements were observed in the placebo arm.
Probiotics ‘hot topic’ among patients
Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen (Germany), said in an interview that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”
Dr. Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.
“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”
The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Dr. Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”
This, she argued, could have resulted in better absorption of levodopa.
A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”
Beyond constipation?
Dr. Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”
Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,’” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.
Veronica Bruno, MD, MPH, assistant professor in the department of clinical neurosciences at the University of Calgary (Alta.), commented in a press release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.
The current study “stands out as a significant contribution to this area of study,” she said.
“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”
Dr. Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”
The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
COPENHAGEN – results of a new randomized trial show.
Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, PhD, department of neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience.
Dr. Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders.
“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Dr. Leta told attendees of the congress.
A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including proinflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”
However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited ... to the treatment of constipation,” she explained.
The team therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.
The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.
A total of 74 patients were randomly assigned to the two study arms. The two groups were well matched for sociodemographics, Parkinson’s disease, and constipation-related characteristics, Dr. Leta reported, and only 3 patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events.”
Increase in healthy bacteria
The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.
The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Dr. Leta said.
This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”
The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the postintervention assessment (P < .027).
There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the postintervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).
This, Dr. Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”
No such significant improvements were observed in the placebo arm.
Probiotics ‘hot topic’ among patients
Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen (Germany), said in an interview that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”
Dr. Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.
“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”
The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Dr. Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”
This, she argued, could have resulted in better absorption of levodopa.
A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”
Beyond constipation?
Dr. Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”
Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,’” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.
Veronica Bruno, MD, MPH, assistant professor in the department of clinical neurosciences at the University of Calgary (Alta.), commented in a press release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.
The current study “stands out as a significant contribution to this area of study,” she said.
“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”
Dr. Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”
The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
COPENHAGEN – results of a new randomized trial show.
Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, PhD, department of neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience.
Dr. Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders.
“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Dr. Leta told attendees of the congress.
A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including proinflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”
However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited ... to the treatment of constipation,” she explained.
The team therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.
The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.
A total of 74 patients were randomly assigned to the two study arms. The two groups were well matched for sociodemographics, Parkinson’s disease, and constipation-related characteristics, Dr. Leta reported, and only 3 patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events.”
Increase in healthy bacteria
The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.
The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Dr. Leta said.
This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”
The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the postintervention assessment (P < .027).
There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the postintervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).
This, Dr. Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”
No such significant improvements were observed in the placebo arm.
Probiotics ‘hot topic’ among patients
Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen (Germany), said in an interview that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”
Dr. Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.
“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”
The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Dr. Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”
This, she argued, could have resulted in better absorption of levodopa.
A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”
Beyond constipation?
Dr. Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”
Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,’” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.
Veronica Bruno, MD, MPH, assistant professor in the department of clinical neurosciences at the University of Calgary (Alta.), commented in a press release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.
The current study “stands out as a significant contribution to this area of study,” she said.
“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”
Dr. Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”
The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
AT MDS 2023
Delaying palliative chemo may improve QoL without affecting survival for asymptomatic patients
TOPLINE:
METHODOLOGY:
- Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
- To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
- Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
- QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.
TAKEAWAY:
- The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
- Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
- In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
- Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.
IN PRACTICE:
There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.
SOURCE:
The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.
LIMITATIONS:
- Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
- Some of the studies were older and employed out-of-date treatment regimens.
- QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.
DISCLOSURES:
The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
- To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
- Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
- QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.
TAKEAWAY:
- The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
- Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
- In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
- Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.
IN PRACTICE:
There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.
SOURCE:
The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.
LIMITATIONS:
- Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
- Some of the studies were older and employed out-of-date treatment regimens.
- QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.
DISCLOSURES:
The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
- To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
- Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
- QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.
TAKEAWAY:
- The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
- Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
- In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
- Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.
IN PRACTICE:
There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.
SOURCE:
The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.
LIMITATIONS:
- Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
- Some of the studies were older and employed out-of-date treatment regimens.
- QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.
DISCLOSURES:
The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.
A version of this article first appeared on Medscape.com.
FROM THE ONCOLOGIST
Financial toxicity screening can reduce cancer cost burdens
TOPLINE:
Patients undergoing systemic therapy for advanced cancer who received monthly screening for financial toxicity for up to 1 year were less likely to develop financial difficulties or have their financial issues get worse.
METHODOLOGY:
- About one in five cancer survivors report experiencing financial toxicity, but financial monitoring is not a routine part of clinical care.
- In the current analysis, researchers evaluated whether screening for financial toxicity during routine care could prevent patients with advanced cancer from developing financial difficulties.
- The study involved 1,191 patients undergoing systemic therapy for metastatic cancer at 52 community oncology practices in the United States. The practices were randomly assigned in a 1:1 ratio to use either digital symptom monitoring through patient-reported outcomes or usual care.
- With the digital monitoring, patients received online or automated telephone surveys between visits inquiring about symptoms, functioning, and financial toxicity for up to 1 year.
- The financial toxicity inquiry consisted of a single-item screening question, scored on a 0-5 scale, from the Functional Assessment of Chronic Illness Therapy COmprehensive Score for financial Toxicity (FACIT-COST): “In the last month, my illness has been a financial hardship to my family and me.” Scores higher than 2, indicating “quite a bit or very much,” triggered an automated alert to practice nurses.
- At different points, patients in both groups also received a question to assess a change in financial difficulties from baseline: “During the past week, has your physical condition or medical treatment caused you financial difficulties?”
TAKEAWAY:
- Among patients receiving financial toxicity screening, 30.2% developed or experienced worsening financial difficulties, compared with 39.0% of those treated at practices without the financial burden screening (P = .004).
- The results corresponded to a number needed to screen of 11.4, meaning that, on average, 11.4 patients would need to be screened for 1 additional patient to avoid developing financial difficulties or having their financial challenges get worse.
- Nurses and patients who were interviewed noted that financial screening helped them identify patients for financial counseling who otherwise may be reluctant to seek or were unaware of such assistance.
- The intervention had a similar positive impact among White patients, men, and women, compared with the overall study population, but appeared to have no effect among Black patients (38% for intervention vs. 39% for the control).
IN PRACTICE:
the authors concluded. Given the relatively low number needed to screen, “financial toxicity screening appears to be a high-yield intervention.”
SOURCE:
The analysis, by Victoria S. Binder, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues was published online in the Journal of Clinical Oncology.
LIMITATIONS:
- The use of a single-item measure could call the replicability of the findings into question.
- Given that the financial toxicity monitoring did not appear to be effective among Black patients, the screening intervention may not adequately address all racial and ethnic groups.
DISCLOSURES:
The trial was sponsored by the Foundation of the Alliance for Clinical Trials in Oncology and was supported in part by a Patient-Centered Outcomes Research Institute Award IHS-1511-33, 392. The authors’ disclosures are detailed in the published study.
A version of this article first appeared on Medscape.com.
TOPLINE:
Patients undergoing systemic therapy for advanced cancer who received monthly screening for financial toxicity for up to 1 year were less likely to develop financial difficulties or have their financial issues get worse.
METHODOLOGY:
- About one in five cancer survivors report experiencing financial toxicity, but financial monitoring is not a routine part of clinical care.
- In the current analysis, researchers evaluated whether screening for financial toxicity during routine care could prevent patients with advanced cancer from developing financial difficulties.
- The study involved 1,191 patients undergoing systemic therapy for metastatic cancer at 52 community oncology practices in the United States. The practices were randomly assigned in a 1:1 ratio to use either digital symptom monitoring through patient-reported outcomes or usual care.
- With the digital monitoring, patients received online or automated telephone surveys between visits inquiring about symptoms, functioning, and financial toxicity for up to 1 year.
- The financial toxicity inquiry consisted of a single-item screening question, scored on a 0-5 scale, from the Functional Assessment of Chronic Illness Therapy COmprehensive Score for financial Toxicity (FACIT-COST): “In the last month, my illness has been a financial hardship to my family and me.” Scores higher than 2, indicating “quite a bit or very much,” triggered an automated alert to practice nurses.
- At different points, patients in both groups also received a question to assess a change in financial difficulties from baseline: “During the past week, has your physical condition or medical treatment caused you financial difficulties?”
TAKEAWAY:
- Among patients receiving financial toxicity screening, 30.2% developed or experienced worsening financial difficulties, compared with 39.0% of those treated at practices without the financial burden screening (P = .004).
- The results corresponded to a number needed to screen of 11.4, meaning that, on average, 11.4 patients would need to be screened for 1 additional patient to avoid developing financial difficulties or having their financial challenges get worse.
- Nurses and patients who were interviewed noted that financial screening helped them identify patients for financial counseling who otherwise may be reluctant to seek or were unaware of such assistance.
- The intervention had a similar positive impact among White patients, men, and women, compared with the overall study population, but appeared to have no effect among Black patients (38% for intervention vs. 39% for the control).
IN PRACTICE:
the authors concluded. Given the relatively low number needed to screen, “financial toxicity screening appears to be a high-yield intervention.”
SOURCE:
The analysis, by Victoria S. Binder, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues was published online in the Journal of Clinical Oncology.
LIMITATIONS:
- The use of a single-item measure could call the replicability of the findings into question.
- Given that the financial toxicity monitoring did not appear to be effective among Black patients, the screening intervention may not adequately address all racial and ethnic groups.
DISCLOSURES:
The trial was sponsored by the Foundation of the Alliance for Clinical Trials in Oncology and was supported in part by a Patient-Centered Outcomes Research Institute Award IHS-1511-33, 392. The authors’ disclosures are detailed in the published study.
A version of this article first appeared on Medscape.com.
TOPLINE:
Patients undergoing systemic therapy for advanced cancer who received monthly screening for financial toxicity for up to 1 year were less likely to develop financial difficulties or have their financial issues get worse.
METHODOLOGY:
- About one in five cancer survivors report experiencing financial toxicity, but financial monitoring is not a routine part of clinical care.
- In the current analysis, researchers evaluated whether screening for financial toxicity during routine care could prevent patients with advanced cancer from developing financial difficulties.
- The study involved 1,191 patients undergoing systemic therapy for metastatic cancer at 52 community oncology practices in the United States. The practices were randomly assigned in a 1:1 ratio to use either digital symptom monitoring through patient-reported outcomes or usual care.
- With the digital monitoring, patients received online or automated telephone surveys between visits inquiring about symptoms, functioning, and financial toxicity for up to 1 year.
- The financial toxicity inquiry consisted of a single-item screening question, scored on a 0-5 scale, from the Functional Assessment of Chronic Illness Therapy COmprehensive Score for financial Toxicity (FACIT-COST): “In the last month, my illness has been a financial hardship to my family and me.” Scores higher than 2, indicating “quite a bit or very much,” triggered an automated alert to practice nurses.
- At different points, patients in both groups also received a question to assess a change in financial difficulties from baseline: “During the past week, has your physical condition or medical treatment caused you financial difficulties?”
TAKEAWAY:
- Among patients receiving financial toxicity screening, 30.2% developed or experienced worsening financial difficulties, compared with 39.0% of those treated at practices without the financial burden screening (P = .004).
- The results corresponded to a number needed to screen of 11.4, meaning that, on average, 11.4 patients would need to be screened for 1 additional patient to avoid developing financial difficulties or having their financial challenges get worse.
- Nurses and patients who were interviewed noted that financial screening helped them identify patients for financial counseling who otherwise may be reluctant to seek or were unaware of such assistance.
- The intervention had a similar positive impact among White patients, men, and women, compared with the overall study population, but appeared to have no effect among Black patients (38% for intervention vs. 39% for the control).
IN PRACTICE:
the authors concluded. Given the relatively low number needed to screen, “financial toxicity screening appears to be a high-yield intervention.”
SOURCE:
The analysis, by Victoria S. Binder, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues was published online in the Journal of Clinical Oncology.
LIMITATIONS:
- The use of a single-item measure could call the replicability of the findings into question.
- Given that the financial toxicity monitoring did not appear to be effective among Black patients, the screening intervention may not adequately address all racial and ethnic groups.
DISCLOSURES:
The trial was sponsored by the Foundation of the Alliance for Clinical Trials in Oncology and was supported in part by a Patient-Centered Outcomes Research Institute Award IHS-1511-33, 392. The authors’ disclosures are detailed in the published study.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Hemophilia: Concizumab lessens bleeding, could expand treatment options
Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.
“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.
The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.
The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).
For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).
The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.
Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.
While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.
Plasma concentrations of concizumab remained stable over the course of the study.
There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
Pause for safety
Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.
The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.
The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
Option for hemophilia B important
Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.
A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.
The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.
As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.
Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.
Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.
“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
FDA resubmission planned
In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.
“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”
Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.
The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.
Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.
“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.
The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.
The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).
For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).
The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.
Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.
While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.
Plasma concentrations of concizumab remained stable over the course of the study.
There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
Pause for safety
Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.
The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.
The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
Option for hemophilia B important
Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.
A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.
The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.
As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.
Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.
Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.
“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
FDA resubmission planned
In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.
“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”
Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.
The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.
Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.
“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.
The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.
The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).
For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).
The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.
Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.
While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.
Plasma concentrations of concizumab remained stable over the course of the study.
There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
Pause for safety
Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.
The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.
The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
Option for hemophilia B important
Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.
A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.
The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.
As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.
Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.
Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.
“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
FDA resubmission planned
In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.
“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”
Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.
The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Making one key connection may increase HPV vax uptake
The understanding that human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC) has been linked with increased likelihood of adults having been vaccinated for HPV, new research indicates.
In a study published online in JAMA Otolaryngology–Head and Neck Surgery, most of the 288 adults surveyed with validated questions were not aware that HPV causes OPSCC and had not been told of the relationship by their health care provider.
Researchers found that when participants knew about the relationship between HPV infection and OPSCC they were more than three times as likely to be vaccinated (odds ratio, 3.7; 95% confidence interval, 1.8-7.6) as those without the knowledge.
The survey was paired with a novel point-of-care adult vaccination program within an otolaryngology clinic.
“Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults,” write the authors, led by Jacob C. Bloom, MD, with the department of otolaryngology–head and neck surgery at Boston Medical Center.
Current HPV vaccination recommendations include three parts:
- Routine vaccination at age 11 or 12 years
- Catch-up vaccination at ages 13-26 years if not adequately vaccinated
- Shared clinical decision-making in adults aged 27-45 years if the vaccine series has not been completed.
Despite proven efficacy and safety of the HPV vaccine, vaccination rates are low for adults. Although 75% of adolescents aged 13-17 years have initiated the HPV vaccine, recent studies show only 16% of U.S. men aged 18-21 years have received at least 1 dose of the HPV vaccine, the authors write.
Christiana Zhang, MD, with the division of internal medicine at Johns Hopkins University in Baltimore, who was not part of the study, said she was not surprised by the lack of knowledge about the HPV-OPSCC link.
Patients are often counseled on the relationship between HPV and genital warts or anogenital cancers like cervical cancer, she says, but there is less patient education surrounding the relationship between HPV and oropharyngeal cancers.
She says she does counsel patients on the link with OPSCC, but not all providers do and provider knowledge in general surrounding HPV is low.
“Research has shown that knowledge and confidence among health care providers surrounding HPV vaccination is generally low, and this corresponds with a low vaccination recommendation rate,” she says.
She adds, “Patient education on HPV infection and its relationship with OPSCC, paired with point-of-care vaccination for qualifying patients, is a great approach.”
But the education needs to go beyond patients, she says.
“Given the important role that health care providers play in vaccine uptake, I think further efforts are needed to educate providers on HPV vaccination as well,” she says.
The study included patients aged 18-45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from Sept. 1, 2020, to May 19, 2021.
Limitations of this study include studying a population from a single otolaryngology clinic in an urban, academic medical center. The population was more racially and ethnically diverse than the U.S. population with 60.3% identifying as racial and ethnic minorities. Gender and educational levels were also not reflective of U.S. demographics as half (50.8%) of the participants had a college degree or higher and 58.3% were women.
Dr. Bloom reports grants from the American Head and Neck Cancer Society during the conduct of the study. Coauthor Dr. Faden reports personal fees from Merck, Neotic, Focus, BMS, Chrystalis Biomedical Advisors, and Guidepoint; receiving nonfinancial support from BostonGene and Predicine; and receiving grants from Calico outside the submitted work. Dr. Zhang reports no relevant financial relationships.
The understanding that human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC) has been linked with increased likelihood of adults having been vaccinated for HPV, new research indicates.
In a study published online in JAMA Otolaryngology–Head and Neck Surgery, most of the 288 adults surveyed with validated questions were not aware that HPV causes OPSCC and had not been told of the relationship by their health care provider.
Researchers found that when participants knew about the relationship between HPV infection and OPSCC they were more than three times as likely to be vaccinated (odds ratio, 3.7; 95% confidence interval, 1.8-7.6) as those without the knowledge.
The survey was paired with a novel point-of-care adult vaccination program within an otolaryngology clinic.
“Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults,” write the authors, led by Jacob C. Bloom, MD, with the department of otolaryngology–head and neck surgery at Boston Medical Center.
Current HPV vaccination recommendations include three parts:
- Routine vaccination at age 11 or 12 years
- Catch-up vaccination at ages 13-26 years if not adequately vaccinated
- Shared clinical decision-making in adults aged 27-45 years if the vaccine series has not been completed.
Despite proven efficacy and safety of the HPV vaccine, vaccination rates are low for adults. Although 75% of adolescents aged 13-17 years have initiated the HPV vaccine, recent studies show only 16% of U.S. men aged 18-21 years have received at least 1 dose of the HPV vaccine, the authors write.
Christiana Zhang, MD, with the division of internal medicine at Johns Hopkins University in Baltimore, who was not part of the study, said she was not surprised by the lack of knowledge about the HPV-OPSCC link.
Patients are often counseled on the relationship between HPV and genital warts or anogenital cancers like cervical cancer, she says, but there is less patient education surrounding the relationship between HPV and oropharyngeal cancers.
She says she does counsel patients on the link with OPSCC, but not all providers do and provider knowledge in general surrounding HPV is low.
“Research has shown that knowledge and confidence among health care providers surrounding HPV vaccination is generally low, and this corresponds with a low vaccination recommendation rate,” she says.
She adds, “Patient education on HPV infection and its relationship with OPSCC, paired with point-of-care vaccination for qualifying patients, is a great approach.”
But the education needs to go beyond patients, she says.
“Given the important role that health care providers play in vaccine uptake, I think further efforts are needed to educate providers on HPV vaccination as well,” she says.
The study included patients aged 18-45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from Sept. 1, 2020, to May 19, 2021.
Limitations of this study include studying a population from a single otolaryngology clinic in an urban, academic medical center. The population was more racially and ethnically diverse than the U.S. population with 60.3% identifying as racial and ethnic minorities. Gender and educational levels were also not reflective of U.S. demographics as half (50.8%) of the participants had a college degree or higher and 58.3% were women.
Dr. Bloom reports grants from the American Head and Neck Cancer Society during the conduct of the study. Coauthor Dr. Faden reports personal fees from Merck, Neotic, Focus, BMS, Chrystalis Biomedical Advisors, and Guidepoint; receiving nonfinancial support from BostonGene and Predicine; and receiving grants from Calico outside the submitted work. Dr. Zhang reports no relevant financial relationships.
The understanding that human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC) has been linked with increased likelihood of adults having been vaccinated for HPV, new research indicates.
In a study published online in JAMA Otolaryngology–Head and Neck Surgery, most of the 288 adults surveyed with validated questions were not aware that HPV causes OPSCC and had not been told of the relationship by their health care provider.
Researchers found that when participants knew about the relationship between HPV infection and OPSCC they were more than three times as likely to be vaccinated (odds ratio, 3.7; 95% confidence interval, 1.8-7.6) as those without the knowledge.
The survey was paired with a novel point-of-care adult vaccination program within an otolaryngology clinic.
“Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults,” write the authors, led by Jacob C. Bloom, MD, with the department of otolaryngology–head and neck surgery at Boston Medical Center.
Current HPV vaccination recommendations include three parts:
- Routine vaccination at age 11 or 12 years
- Catch-up vaccination at ages 13-26 years if not adequately vaccinated
- Shared clinical decision-making in adults aged 27-45 years if the vaccine series has not been completed.
Despite proven efficacy and safety of the HPV vaccine, vaccination rates are low for adults. Although 75% of adolescents aged 13-17 years have initiated the HPV vaccine, recent studies show only 16% of U.S. men aged 18-21 years have received at least 1 dose of the HPV vaccine, the authors write.
Christiana Zhang, MD, with the division of internal medicine at Johns Hopkins University in Baltimore, who was not part of the study, said she was not surprised by the lack of knowledge about the HPV-OPSCC link.
Patients are often counseled on the relationship between HPV and genital warts or anogenital cancers like cervical cancer, she says, but there is less patient education surrounding the relationship between HPV and oropharyngeal cancers.
She says she does counsel patients on the link with OPSCC, but not all providers do and provider knowledge in general surrounding HPV is low.
“Research has shown that knowledge and confidence among health care providers surrounding HPV vaccination is generally low, and this corresponds with a low vaccination recommendation rate,” she says.
She adds, “Patient education on HPV infection and its relationship with OPSCC, paired with point-of-care vaccination for qualifying patients, is a great approach.”
But the education needs to go beyond patients, she says.
“Given the important role that health care providers play in vaccine uptake, I think further efforts are needed to educate providers on HPV vaccination as well,” she says.
The study included patients aged 18-45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from Sept. 1, 2020, to May 19, 2021.
Limitations of this study include studying a population from a single otolaryngology clinic in an urban, academic medical center. The population was more racially and ethnically diverse than the U.S. population with 60.3% identifying as racial and ethnic minorities. Gender and educational levels were also not reflective of U.S. demographics as half (50.8%) of the participants had a college degree or higher and 58.3% were women.
Dr. Bloom reports grants from the American Head and Neck Cancer Society during the conduct of the study. Coauthor Dr. Faden reports personal fees from Merck, Neotic, Focus, BMS, Chrystalis Biomedical Advisors, and Guidepoint; receiving nonfinancial support from BostonGene and Predicine; and receiving grants from Calico outside the submitted work. Dr. Zhang reports no relevant financial relationships.
FROM JAMA OTOLARYNGOLOGY–HEAD AND NECK SURGERY
Industry funding falls for rheumatology research
Industry-sponsored research funding has fallen by more than 20% from 2014 to 2022, according to a new analysis.
“Despite the growing partnerships and networks between rheumatologists, the public sector, and the health care industry to optimize research funding allocations, the declining trend in industry-sponsored research payments is a concerning sign for all rheumatologists,” writes study author Anju Murayama, an undergraduate medical student at the Tohoku University School of Medicine in Sendai City, Japan. The data suggest that “more and more rheumatologists are facing difficulties in obtaining research funding from the health care industry.”
Dr. Murayama used the Open Payments Database, which contains records of payments made by drug and pharmaceutical companies to health care providers. The analysis included research payments provided directly to rheumatologists (direct-research payments) and payments given to clinicians or health care organizations related to research whose principal investigator was a rheumatologist (associated-research payments). These associated payments included costs for study enrollment and screening, safety monitoring committees, research publication, and more.
The research was published August 15 in The Journal of Rheumatology .
In 2014, the total direct payments to rheumatologists from industry were $1.4 million. These payments jumped to nearly $4.6 million in 2016 but have declined since. In 2022, there were $976,481 in total payments, a 31% drop from 9 years before.
This decline comes after an observed drop in research funding from the public sector. From 2014 to 2017, public-sector research funding to members of the American College of Rheumatology fell by 7.5%. Timothy Niewold, MD, a rheumatologist and vice chair for research in the department of medicine at Hospital for Special Surgery, New York, said that he and colleagues have felt the funding squeeze from both public and industry sectors. “The budgets for trials have seemed tight,” he told this news organization. With the overhead and cost of doing a trial at an academic institution like HSS, “sometimes you can’t make the budget work,” and researchers must pass on industry-funded trials.
The analysis also found a larger discrepancy between average and median associated-research payments. Of the $1.4 billion in associated-research payments combined over the 9-year period, the median payments per physician ($173,022) were much smaller than the mean payments ($989,753), which indicates that “only a very small number of rheumatologists received substantial amounts of research funding from the industry,” Dr. Murayama wrote in an email to this news organization. “This finding might support statements published by Scher and Schett in Nature Review Rheumatology suggesting that many industry-initiated clinical trials are conducted and authored by a small number of influential rheumatologists, often referred to as key opinion leaders.”
The analysis also found that of all associated payments, less than 3% ($39.2 million) went to funding preclinical research, which is “more disappointing than surprising,” Dr. Niewold said. Though clinical trials are expensive and require larger amounts of investment, industry partnerships at preclinical phases of research are important for devising novel solutions for these complex rheumatic diseases, he noted. “The clinical trials are one piece,” he added, “but you need the whole [research] continuum.”
Dr. Niewold reports receiving research grants from EMD Serono and Zenas Biopharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, Ventus, S3 Connected Health, AstraZeneca, and Inova. Dr. Murayama reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Industry-sponsored research funding has fallen by more than 20% from 2014 to 2022, according to a new analysis.
“Despite the growing partnerships and networks between rheumatologists, the public sector, and the health care industry to optimize research funding allocations, the declining trend in industry-sponsored research payments is a concerning sign for all rheumatologists,” writes study author Anju Murayama, an undergraduate medical student at the Tohoku University School of Medicine in Sendai City, Japan. The data suggest that “more and more rheumatologists are facing difficulties in obtaining research funding from the health care industry.”
Dr. Murayama used the Open Payments Database, which contains records of payments made by drug and pharmaceutical companies to health care providers. The analysis included research payments provided directly to rheumatologists (direct-research payments) and payments given to clinicians or health care organizations related to research whose principal investigator was a rheumatologist (associated-research payments). These associated payments included costs for study enrollment and screening, safety monitoring committees, research publication, and more.
The research was published August 15 in The Journal of Rheumatology .
In 2014, the total direct payments to rheumatologists from industry were $1.4 million. These payments jumped to nearly $4.6 million in 2016 but have declined since. In 2022, there were $976,481 in total payments, a 31% drop from 9 years before.
This decline comes after an observed drop in research funding from the public sector. From 2014 to 2017, public-sector research funding to members of the American College of Rheumatology fell by 7.5%. Timothy Niewold, MD, a rheumatologist and vice chair for research in the department of medicine at Hospital for Special Surgery, New York, said that he and colleagues have felt the funding squeeze from both public and industry sectors. “The budgets for trials have seemed tight,” he told this news organization. With the overhead and cost of doing a trial at an academic institution like HSS, “sometimes you can’t make the budget work,” and researchers must pass on industry-funded trials.
The analysis also found a larger discrepancy between average and median associated-research payments. Of the $1.4 billion in associated-research payments combined over the 9-year period, the median payments per physician ($173,022) were much smaller than the mean payments ($989,753), which indicates that “only a very small number of rheumatologists received substantial amounts of research funding from the industry,” Dr. Murayama wrote in an email to this news organization. “This finding might support statements published by Scher and Schett in Nature Review Rheumatology suggesting that many industry-initiated clinical trials are conducted and authored by a small number of influential rheumatologists, often referred to as key opinion leaders.”
The analysis also found that of all associated payments, less than 3% ($39.2 million) went to funding preclinical research, which is “more disappointing than surprising,” Dr. Niewold said. Though clinical trials are expensive and require larger amounts of investment, industry partnerships at preclinical phases of research are important for devising novel solutions for these complex rheumatic diseases, he noted. “The clinical trials are one piece,” he added, “but you need the whole [research] continuum.”
Dr. Niewold reports receiving research grants from EMD Serono and Zenas Biopharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, Ventus, S3 Connected Health, AstraZeneca, and Inova. Dr. Murayama reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Industry-sponsored research funding has fallen by more than 20% from 2014 to 2022, according to a new analysis.
“Despite the growing partnerships and networks between rheumatologists, the public sector, and the health care industry to optimize research funding allocations, the declining trend in industry-sponsored research payments is a concerning sign for all rheumatologists,” writes study author Anju Murayama, an undergraduate medical student at the Tohoku University School of Medicine in Sendai City, Japan. The data suggest that “more and more rheumatologists are facing difficulties in obtaining research funding from the health care industry.”
Dr. Murayama used the Open Payments Database, which contains records of payments made by drug and pharmaceutical companies to health care providers. The analysis included research payments provided directly to rheumatologists (direct-research payments) and payments given to clinicians or health care organizations related to research whose principal investigator was a rheumatologist (associated-research payments). These associated payments included costs for study enrollment and screening, safety monitoring committees, research publication, and more.
The research was published August 15 in The Journal of Rheumatology .
In 2014, the total direct payments to rheumatologists from industry were $1.4 million. These payments jumped to nearly $4.6 million in 2016 but have declined since. In 2022, there were $976,481 in total payments, a 31% drop from 9 years before.
This decline comes after an observed drop in research funding from the public sector. From 2014 to 2017, public-sector research funding to members of the American College of Rheumatology fell by 7.5%. Timothy Niewold, MD, a rheumatologist and vice chair for research in the department of medicine at Hospital for Special Surgery, New York, said that he and colleagues have felt the funding squeeze from both public and industry sectors. “The budgets for trials have seemed tight,” he told this news organization. With the overhead and cost of doing a trial at an academic institution like HSS, “sometimes you can’t make the budget work,” and researchers must pass on industry-funded trials.
The analysis also found a larger discrepancy between average and median associated-research payments. Of the $1.4 billion in associated-research payments combined over the 9-year period, the median payments per physician ($173,022) were much smaller than the mean payments ($989,753), which indicates that “only a very small number of rheumatologists received substantial amounts of research funding from the industry,” Dr. Murayama wrote in an email to this news organization. “This finding might support statements published by Scher and Schett in Nature Review Rheumatology suggesting that many industry-initiated clinical trials are conducted and authored by a small number of influential rheumatologists, often referred to as key opinion leaders.”
The analysis also found that of all associated payments, less than 3% ($39.2 million) went to funding preclinical research, which is “more disappointing than surprising,” Dr. Niewold said. Though clinical trials are expensive and require larger amounts of investment, industry partnerships at preclinical phases of research are important for devising novel solutions for these complex rheumatic diseases, he noted. “The clinical trials are one piece,” he added, “but you need the whole [research] continuum.”
Dr. Niewold reports receiving research grants from EMD Serono and Zenas Biopharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, Ventus, S3 Connected Health, AstraZeneca, and Inova. Dr. Murayama reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF RHEUMATOLOGY
FDA approves canakinumab for gout flares
The U.S. Food and Drug Administration has approved canakinumab (Ilaris) for the treatment of gout flares in adults who cannot be treated with NSAIDs, colchicine, or repeated courses of corticosteroids. The drug is also indicated for people who could not tolerate or had an inadequate response to NSAIDs or colchicine.
The drug, a humanized anti–interleukin-1 beta monoclonal antibody, is the first and only biologic approved in the United States for the treatment of gout flares, according to Novartis. It is administered in a single, subcutaneous injection of 150 mg.
“At Novartis, we are committed to bringing medicines that address high unmet needs to patients. We are proud to receive approval on our eighth indication for Ilaris in the U.S. and provide the first biologic medicine option for people with gout flares to help treat this painful and debilitating condition,” the company said in a statement to this news organization.
Canakinumab was first approved in the United States in 2009 for the treatment of children and adults with cryopyrin-associated periodic syndrome (CAPS). Since then, it has been approved for the treatment of several other autoinflammatory diseases, including Still’s disease and recurrent fever syndromes.
In 2011, an FDA advisory panel voted against the approval of canakinumab to treat acute gout flares refractory to NSAIDs, colchicine, or repeated courses of corticosteroids, while in 2013, the European Medicine Agency approved the drug for this treatment indication.
Since that FDA advisory committee meeting and the FDA’s subsequent rejection letter, “[Novartis] has conducted additional studies in patients with gout flares and other related populations to further characterize the short- and long-term safety of canakinumab supporting the current application. To further support the benefit-risk [profile of the drug], the indication is for a more restricted population than initially proposed in 2011,” the FDA’s Center for Drug Evaluation and Research said in a statement to this news organization. “Given these considerations and the available safety information, the Agency determined that canakinumab, at the recommended dosage, has a favorable risk-benefit profile” in the specified patient population.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved canakinumab (Ilaris) for the treatment of gout flares in adults who cannot be treated with NSAIDs, colchicine, or repeated courses of corticosteroids. The drug is also indicated for people who could not tolerate or had an inadequate response to NSAIDs or colchicine.
The drug, a humanized anti–interleukin-1 beta monoclonal antibody, is the first and only biologic approved in the United States for the treatment of gout flares, according to Novartis. It is administered in a single, subcutaneous injection of 150 mg.
“At Novartis, we are committed to bringing medicines that address high unmet needs to patients. We are proud to receive approval on our eighth indication for Ilaris in the U.S. and provide the first biologic medicine option for people with gout flares to help treat this painful and debilitating condition,” the company said in a statement to this news organization.
Canakinumab was first approved in the United States in 2009 for the treatment of children and adults with cryopyrin-associated periodic syndrome (CAPS). Since then, it has been approved for the treatment of several other autoinflammatory diseases, including Still’s disease and recurrent fever syndromes.
In 2011, an FDA advisory panel voted against the approval of canakinumab to treat acute gout flares refractory to NSAIDs, colchicine, or repeated courses of corticosteroids, while in 2013, the European Medicine Agency approved the drug for this treatment indication.
Since that FDA advisory committee meeting and the FDA’s subsequent rejection letter, “[Novartis] has conducted additional studies in patients with gout flares and other related populations to further characterize the short- and long-term safety of canakinumab supporting the current application. To further support the benefit-risk [profile of the drug], the indication is for a more restricted population than initially proposed in 2011,” the FDA’s Center for Drug Evaluation and Research said in a statement to this news organization. “Given these considerations and the available safety information, the Agency determined that canakinumab, at the recommended dosage, has a favorable risk-benefit profile” in the specified patient population.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved canakinumab (Ilaris) for the treatment of gout flares in adults who cannot be treated with NSAIDs, colchicine, or repeated courses of corticosteroids. The drug is also indicated for people who could not tolerate or had an inadequate response to NSAIDs or colchicine.
The drug, a humanized anti–interleukin-1 beta monoclonal antibody, is the first and only biologic approved in the United States for the treatment of gout flares, according to Novartis. It is administered in a single, subcutaneous injection of 150 mg.
“At Novartis, we are committed to bringing medicines that address high unmet needs to patients. We are proud to receive approval on our eighth indication for Ilaris in the U.S. and provide the first biologic medicine option for people with gout flares to help treat this painful and debilitating condition,” the company said in a statement to this news organization.
Canakinumab was first approved in the United States in 2009 for the treatment of children and adults with cryopyrin-associated periodic syndrome (CAPS). Since then, it has been approved for the treatment of several other autoinflammatory diseases, including Still’s disease and recurrent fever syndromes.
In 2011, an FDA advisory panel voted against the approval of canakinumab to treat acute gout flares refractory to NSAIDs, colchicine, or repeated courses of corticosteroids, while in 2013, the European Medicine Agency approved the drug for this treatment indication.
Since that FDA advisory committee meeting and the FDA’s subsequent rejection letter, “[Novartis] has conducted additional studies in patients with gout flares and other related populations to further characterize the short- and long-term safety of canakinumab supporting the current application. To further support the benefit-risk [profile of the drug], the indication is for a more restricted population than initially proposed in 2011,” the FDA’s Center for Drug Evaluation and Research said in a statement to this news organization. “Given these considerations and the available safety information, the Agency determined that canakinumab, at the recommended dosage, has a favorable risk-benefit profile” in the specified patient population.
A version of this article first appeared on Medscape.com.
Raised Linear Plaques on the Back
The Diagnosis: Flagellate Dermatitis
Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.
Flagellate dermatitis usually appears on the torso as linear whiplike streaks.1 The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.2
Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.3 Flagellate dermatitis also is seen in some patients with dermatomyositis.4 A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.
Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.6 Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.6
In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.
- Biswas A, Chaudhari PB, Sharma P, et al. Bleomycin induced flagellate erythema: revisiting a unique complication. J Cancer Res Ther. 2013;9:500-503.
- Yagoda A, Mukherji B, Young C, et al. Bleomycin, an anti-tumor antibiotic: clinical experience in 274 patients. Ann Intern Med. 1972;77:861-870.
- Cohen PR. Trastuzumab-associated flagellate erythema: report in a woman with metastatic breast cancer and review of antineoplastic therapy-induced flagellate dermatoses. Dermatol Ther (Heidelb). 2015;5:253-264. doi:10.1007/s13555-015-0085-2
- Grynszpan R, Niemeyer-Corbellini JP, Lopes MS, et al. Bleomycininduced flagellate dermatitis. BMJ Case Rep. 2013;2013:bcr2013009764. doi:10.1136/bcr-2013-009764
- Stephany MP, Chung S, Handler MZ, et al. Shiitake mushroom dermatitis: a review. Am J Clin Dermatol. 2016;17:485-489.
- Boels D, Landreau A, Bruneau C, et al. Shiitake dermatitis recorded by French Poison Control Centers—new case series with clinical observations. Clin Toxicol (Phila). 2014;52:625-628.
The Diagnosis: Flagellate Dermatitis
Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.
Flagellate dermatitis usually appears on the torso as linear whiplike streaks.1 The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.2
Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.3 Flagellate dermatitis also is seen in some patients with dermatomyositis.4 A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.
Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.6 Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.6
In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.
The Diagnosis: Flagellate Dermatitis
Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.
Flagellate dermatitis usually appears on the torso as linear whiplike streaks.1 The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.2
Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.3 Flagellate dermatitis also is seen in some patients with dermatomyositis.4 A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.
Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.6 Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.6
In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.
- Biswas A, Chaudhari PB, Sharma P, et al. Bleomycin induced flagellate erythema: revisiting a unique complication. J Cancer Res Ther. 2013;9:500-503.
- Yagoda A, Mukherji B, Young C, et al. Bleomycin, an anti-tumor antibiotic: clinical experience in 274 patients. Ann Intern Med. 1972;77:861-870.
- Cohen PR. Trastuzumab-associated flagellate erythema: report in a woman with metastatic breast cancer and review of antineoplastic therapy-induced flagellate dermatoses. Dermatol Ther (Heidelb). 2015;5:253-264. doi:10.1007/s13555-015-0085-2
- Grynszpan R, Niemeyer-Corbellini JP, Lopes MS, et al. Bleomycininduced flagellate dermatitis. BMJ Case Rep. 2013;2013:bcr2013009764. doi:10.1136/bcr-2013-009764
- Stephany MP, Chung S, Handler MZ, et al. Shiitake mushroom dermatitis: a review. Am J Clin Dermatol. 2016;17:485-489.
- Boels D, Landreau A, Bruneau C, et al. Shiitake dermatitis recorded by French Poison Control Centers—new case series with clinical observations. Clin Toxicol (Phila). 2014;52:625-628.
- Biswas A, Chaudhari PB, Sharma P, et al. Bleomycin induced flagellate erythema: revisiting a unique complication. J Cancer Res Ther. 2013;9:500-503.
- Yagoda A, Mukherji B, Young C, et al. Bleomycin, an anti-tumor antibiotic: clinical experience in 274 patients. Ann Intern Med. 1972;77:861-870.
- Cohen PR. Trastuzumab-associated flagellate erythema: report in a woman with metastatic breast cancer and review of antineoplastic therapy-induced flagellate dermatoses. Dermatol Ther (Heidelb). 2015;5:253-264. doi:10.1007/s13555-015-0085-2
- Grynszpan R, Niemeyer-Corbellini JP, Lopes MS, et al. Bleomycininduced flagellate dermatitis. BMJ Case Rep. 2013;2013:bcr2013009764. doi:10.1136/bcr-2013-009764
- Stephany MP, Chung S, Handler MZ, et al. Shiitake mushroom dermatitis: a review. Am J Clin Dermatol. 2016;17:485-489.
- Boels D, Landreau A, Bruneau C, et al. Shiitake dermatitis recorded by French Poison Control Centers—new case series with clinical observations. Clin Toxicol (Phila). 2014;52:625-628.
A 77-year-old man with a history of hypertension, hyperlipidemia, and nonmelanoma skin cancer presented to the dermatology clinic for evaluation of a new rash of 2 days’ duration. He trialed a previously prescribed triamcinolone cream 0.1% without improvement. The patient denied any recent travel, as well as fever, nausea, vomiting, or changes in bowel habits. Physical examination revealed diffuse, erythematous, raised, linear plaques on the mid to lower back.
Parity for prompt and staged STEMI complete revascularization: MULTISTARS-AMI
The conclusion comes from a randomized outcomes trial of 840 patients that compared prompt same-session CR with a staged procedure carried out weeks later.
That CR is a worthy goal in such cases is largely settled, unlike the question of when to pursue revascularization of nonculprit lesions for best results. So the timing varies in practice, often depending on the patient’s clinical stability, risk status, or practical issues like cath lab resources or personnel.
The new trial, MULTISTARS-AMI, supports that kind of flexibility as safe in practice. Immediate, same-session CR led to a 48% drop in risk for a broad composite primary endpoint at 1 year, compared with staged CR an average of 37 days later. The finding was significant for noninferiority in the study’s primary analysis and secondarily, was significant for superiority (P < .001 in both cases).
The composite endpoint included death from any cause, MI, stroke, unplanned ischemia-driven revascularization, or heart failure (HF) hospitalization.
CR’s immediate effect on outcomes was numerically pronounced, but because it was prespecified as a noninferiority trial, MULTISTARS-AMI could show only that the strategy is comparable to staged CR, emphasized Barbara E. Stähli, MD, MPH, MBA, at a press conference.
Still, it appears to be the first trial of its kind to show that operators and patients can safely choose either percutaneous coronary intervention (PCI) approach and attain similar outcomes, said Dr. Stähli, University Hospital Zurich, MULTISTARS-AMI’s principal investigator.
Not only were the two approaches similar with respect to safety, she noted, but immediate CR seemed to require less use of contrast agent and fluoroscopy. “And you have only one procedure, so there’s only one arterial puncture.”
Dr. Stähli formally presented MULTISTARS-AMI at the annual congress of the European Society of Cardiology, held in Amsterdam. She is also lead author on its publication in the New England Journal of Medicine.
After her presentation, invited discussant Robert A. Byrne, PhD, MD, MB, BCh, said that the trial’s central message is that STEMI patients with MVD having primary PCI “should undergo complete revascularization within the first 45 days, with the timing of the non–infarct-related artery procedure individualized according to clinical risk and logistical considerations.”
Still, the trial “provides evidence, but not strong evidence, of benefits with routine immediate PCI during the index procedure as compared with staged outpatient PCI,” said Dr. Byrne, Mater Private Hospital and RCSI University of Medicine and Health Sciences, Dublin.
MULTISTARS-AMI randomly assigned patients at 37 European sites to undergo same-session CR (418 patients) or CR staged 19-45 days later (422 patients).
Rates for the primary endpoint at 1 year were 8.5% and 16.3%, respectively, for a risk ratio of 0.52 (95% confidence interval, 0.38-0.72). The difference was driven by fewer instances of nonfatal MI, 0.36 (95% CI, 0.16-0.80), and unplanned ischemia-driven revascularization, 0.42 (95% CI, 0.24-0.74), in the immediate-CR group.
The wee hours
Sunil V. Rao, MD, director of interventional cardiology at NYU Langone Health System, New York, said that, in general at his center, patients who are stable with a good primary PCI outcome and whose lesions aren’t very high risk are often discharged to return later for the staged CR procedure.
But after the new insights from MULTISTARS-AMI, Dr. Rao, who is not connected to the study, said in an interview that immediate same-session CR is indeed likely preferable to staged CR performed weeks later.
Same-session CR, however, may not always be practical or wise, he observed. For example, some patients with STEMI can be pretty sick with MVD that involves very complex lesions that might be better handled later.
“The wee hours of the night may not be the best time to tackle such complex lesions,” Dr. Rao observed. If confronted with, for example, a bifurcation that requires a complex procedure, “2 o’clock in the morning is probably not the best time to address something like that.”
So the trial’s more realistic translational message, he proposed, may be to perform CR after the primary PCI but during the same hospitalization, “unless there are some real mitigating circumstances.”
The trial was supported by Boston Scientific. Dr. Stähli had no disclosures. Dr. Byrne discloses research funding to his institution from Abbott Vascular, Translumina, Biosensors, and Boston Scientific. Dr. Rao had no relevant disclosures.
A version of this article first appeared on Medscape.com.
The conclusion comes from a randomized outcomes trial of 840 patients that compared prompt same-session CR with a staged procedure carried out weeks later.
That CR is a worthy goal in such cases is largely settled, unlike the question of when to pursue revascularization of nonculprit lesions for best results. So the timing varies in practice, often depending on the patient’s clinical stability, risk status, or practical issues like cath lab resources or personnel.
The new trial, MULTISTARS-AMI, supports that kind of flexibility as safe in practice. Immediate, same-session CR led to a 48% drop in risk for a broad composite primary endpoint at 1 year, compared with staged CR an average of 37 days later. The finding was significant for noninferiority in the study’s primary analysis and secondarily, was significant for superiority (P < .001 in both cases).
The composite endpoint included death from any cause, MI, stroke, unplanned ischemia-driven revascularization, or heart failure (HF) hospitalization.
CR’s immediate effect on outcomes was numerically pronounced, but because it was prespecified as a noninferiority trial, MULTISTARS-AMI could show only that the strategy is comparable to staged CR, emphasized Barbara E. Stähli, MD, MPH, MBA, at a press conference.
Still, it appears to be the first trial of its kind to show that operators and patients can safely choose either percutaneous coronary intervention (PCI) approach and attain similar outcomes, said Dr. Stähli, University Hospital Zurich, MULTISTARS-AMI’s principal investigator.
Not only were the two approaches similar with respect to safety, she noted, but immediate CR seemed to require less use of contrast agent and fluoroscopy. “And you have only one procedure, so there’s only one arterial puncture.”
Dr. Stähli formally presented MULTISTARS-AMI at the annual congress of the European Society of Cardiology, held in Amsterdam. She is also lead author on its publication in the New England Journal of Medicine.
After her presentation, invited discussant Robert A. Byrne, PhD, MD, MB, BCh, said that the trial’s central message is that STEMI patients with MVD having primary PCI “should undergo complete revascularization within the first 45 days, with the timing of the non–infarct-related artery procedure individualized according to clinical risk and logistical considerations.”
Still, the trial “provides evidence, but not strong evidence, of benefits with routine immediate PCI during the index procedure as compared with staged outpatient PCI,” said Dr. Byrne, Mater Private Hospital and RCSI University of Medicine and Health Sciences, Dublin.
MULTISTARS-AMI randomly assigned patients at 37 European sites to undergo same-session CR (418 patients) or CR staged 19-45 days later (422 patients).
Rates for the primary endpoint at 1 year were 8.5% and 16.3%, respectively, for a risk ratio of 0.52 (95% confidence interval, 0.38-0.72). The difference was driven by fewer instances of nonfatal MI, 0.36 (95% CI, 0.16-0.80), and unplanned ischemia-driven revascularization, 0.42 (95% CI, 0.24-0.74), in the immediate-CR group.
The wee hours
Sunil V. Rao, MD, director of interventional cardiology at NYU Langone Health System, New York, said that, in general at his center, patients who are stable with a good primary PCI outcome and whose lesions aren’t very high risk are often discharged to return later for the staged CR procedure.
But after the new insights from MULTISTARS-AMI, Dr. Rao, who is not connected to the study, said in an interview that immediate same-session CR is indeed likely preferable to staged CR performed weeks later.
Same-session CR, however, may not always be practical or wise, he observed. For example, some patients with STEMI can be pretty sick with MVD that involves very complex lesions that might be better handled later.
“The wee hours of the night may not be the best time to tackle such complex lesions,” Dr. Rao observed. If confronted with, for example, a bifurcation that requires a complex procedure, “2 o’clock in the morning is probably not the best time to address something like that.”
So the trial’s more realistic translational message, he proposed, may be to perform CR after the primary PCI but during the same hospitalization, “unless there are some real mitigating circumstances.”
The trial was supported by Boston Scientific. Dr. Stähli had no disclosures. Dr. Byrne discloses research funding to his institution from Abbott Vascular, Translumina, Biosensors, and Boston Scientific. Dr. Rao had no relevant disclosures.
A version of this article first appeared on Medscape.com.
The conclusion comes from a randomized outcomes trial of 840 patients that compared prompt same-session CR with a staged procedure carried out weeks later.
That CR is a worthy goal in such cases is largely settled, unlike the question of when to pursue revascularization of nonculprit lesions for best results. So the timing varies in practice, often depending on the patient’s clinical stability, risk status, or practical issues like cath lab resources or personnel.
The new trial, MULTISTARS-AMI, supports that kind of flexibility as safe in practice. Immediate, same-session CR led to a 48% drop in risk for a broad composite primary endpoint at 1 year, compared with staged CR an average of 37 days later. The finding was significant for noninferiority in the study’s primary analysis and secondarily, was significant for superiority (P < .001 in both cases).
The composite endpoint included death from any cause, MI, stroke, unplanned ischemia-driven revascularization, or heart failure (HF) hospitalization.
CR’s immediate effect on outcomes was numerically pronounced, but because it was prespecified as a noninferiority trial, MULTISTARS-AMI could show only that the strategy is comparable to staged CR, emphasized Barbara E. Stähli, MD, MPH, MBA, at a press conference.
Still, it appears to be the first trial of its kind to show that operators and patients can safely choose either percutaneous coronary intervention (PCI) approach and attain similar outcomes, said Dr. Stähli, University Hospital Zurich, MULTISTARS-AMI’s principal investigator.
Not only were the two approaches similar with respect to safety, she noted, but immediate CR seemed to require less use of contrast agent and fluoroscopy. “And you have only one procedure, so there’s only one arterial puncture.”
Dr. Stähli formally presented MULTISTARS-AMI at the annual congress of the European Society of Cardiology, held in Amsterdam. She is also lead author on its publication in the New England Journal of Medicine.
After her presentation, invited discussant Robert A. Byrne, PhD, MD, MB, BCh, said that the trial’s central message is that STEMI patients with MVD having primary PCI “should undergo complete revascularization within the first 45 days, with the timing of the non–infarct-related artery procedure individualized according to clinical risk and logistical considerations.”
Still, the trial “provides evidence, but not strong evidence, of benefits with routine immediate PCI during the index procedure as compared with staged outpatient PCI,” said Dr. Byrne, Mater Private Hospital and RCSI University of Medicine and Health Sciences, Dublin.
MULTISTARS-AMI randomly assigned patients at 37 European sites to undergo same-session CR (418 patients) or CR staged 19-45 days later (422 patients).
Rates for the primary endpoint at 1 year were 8.5% and 16.3%, respectively, for a risk ratio of 0.52 (95% confidence interval, 0.38-0.72). The difference was driven by fewer instances of nonfatal MI, 0.36 (95% CI, 0.16-0.80), and unplanned ischemia-driven revascularization, 0.42 (95% CI, 0.24-0.74), in the immediate-CR group.
The wee hours
Sunil V. Rao, MD, director of interventional cardiology at NYU Langone Health System, New York, said that, in general at his center, patients who are stable with a good primary PCI outcome and whose lesions aren’t very high risk are often discharged to return later for the staged CR procedure.
But after the new insights from MULTISTARS-AMI, Dr. Rao, who is not connected to the study, said in an interview that immediate same-session CR is indeed likely preferable to staged CR performed weeks later.
Same-session CR, however, may not always be practical or wise, he observed. For example, some patients with STEMI can be pretty sick with MVD that involves very complex lesions that might be better handled later.
“The wee hours of the night may not be the best time to tackle such complex lesions,” Dr. Rao observed. If confronted with, for example, a bifurcation that requires a complex procedure, “2 o’clock in the morning is probably not the best time to address something like that.”
So the trial’s more realistic translational message, he proposed, may be to perform CR after the primary PCI but during the same hospitalization, “unless there are some real mitigating circumstances.”
The trial was supported by Boston Scientific. Dr. Stähli had no disclosures. Dr. Byrne discloses research funding to his institution from Abbott Vascular, Translumina, Biosensors, and Boston Scientific. Dr. Rao had no relevant disclosures.
A version of this article first appeared on Medscape.com.
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