ORLANDO – The oral iron chelator deferiprone showed noninferiority to deferoxamine for treating iron overload in patients with sickle cell disease and other rare anemias in a randomized open-label trial.

The least squares mean change from baseline in liver iron concentration (LIC) – the primary study endpoint – was –4.04 mg/g dry weight (dw) in 152 patients randomized to receive deferiprone, and –4.45 mg/g dw in 76 who received deferoxamine, Janet L. Kwiatkowski, MD, of the Children’s Hospital of Philadelphia reported at the annual meeting of the American Society of Hematology.

The upper limit of the stringent 96.01% confidence interval used for the evaluation of noninferiority in the study was 1.57, thus the findings demonstrated noninferiority of deferiprone, Dr. Kwiatkowski said.

Deferiprone also showed noninferiority for the secondary endpoints of change in cardiac iron (about –0.02 ms on T2* MRI, log-transformed for both groups) and serum ferritin levels (–415 vs. –750 mcg/L for deferiprone vs. deferoxamine) at 12 months. The difference between the groups was not statistically significant for either endpoint.

Study participants, who had a mean age of 16.9 years, were aged 2 years and older with LIC between 7 and 30 mg/g dw. They were recruited from 33 sites in nine countries and randomized 2:1 to receive deferiprone or deferoxamine for up to 12 months; in patients with lower transfusional iron input and/or less severe iron load, deferiprone was dosed at 75 mg/kg daily and deferoxamine was dosed at 20 mg/kg for children and 40 mg/kg for adults. In those with higher iron input and/or more severe iron load, the deferiprone dose was 99 mg/kg daily and the deferoxamine doses were up to 40 mg/kg in children and up to 50 mg/kg for adults.

“Over the course of the treatment period, the dosage could be adjusted downward if there were side effects, or upward if there was no improvement in iron burden,” Dr Kwiatkowski said, adding that after 12 months, patients had the option of continuing on to a 2-year extension trial in which everyone received deferiprone.

No significant demographic differences were noted between the groups; 84% in both groups had sickle cell disease, and the remaining patients had other, rarer forms of transfusion-dependent anemia. Baseline iron burden was similar in the groups.

The rates of acceptable compliance over the course of the study were also similar at 69% and 79% in the deferiprone and deferoxamine arms, respectively, she noted.

No statistically significant difference between the groups was seen in the overall rate of adverse events, treatment-related AEs, serious AEs, or withdrawals from the study due to AEs. Agranulocytosis occurred in one deferiprone patient and zero deferoxamine patients, and mild or moderate neutropenia occurred in four patients and one patient in the groups, respectively.

All episodes resolved, no difference was seen in the rates of any of the serious AEs, and no unexpected serious adverse events occurred, she said.

Patients with sickle cell disease or other rare anemias whose care includes chronic blood transfusions require iron chelation to prevent iron overload. Currently, only deferoxamine and deferasirox are approved chelators in these patient populations, she said, noting that in 2011 deferiprone received accelerated Food and Drug Administration approval for the treatment of thalassemia.

The current study was conducted because of an FDA requirement for postmarket assessment of deferiprone’s efficacy and safety in patients with sickle cell disease and other anemias who develop transfusional iron overload. It was initiated prior to the approval of deferasirox for the first-line treatment of SCD, therefore it was compared only with deferoxamine, she explained.

Dr. Kwiatkowski reported research funding from Apopharma, bluebird bio, Novartis, and Terumo, and consultancy for Agios, bluebird bio, Celgene, and Imara.

sworcester@mdedge.com

ORLANDO – The oral iron chelator deferiprone showed noninferiority to deferoxamine for treating iron overload in patients with sickle cell disease and other rare anemias in a randomized open-label trial.

The least squares mean change from baseline in liver iron concentration (LIC) – the primary study endpoint – was –4.04 mg/g dry weight (dw) in 152 patients randomized to receive deferiprone, and –4.45 mg/g dw in 76 who received deferoxamine, Janet L. Kwiatkowski, MD, of the Children’s Hospital of Philadelphia reported at the annual meeting of the American Society of Hematology.

The upper limit of the stringent 96.01% confidence interval used for the evaluation of noninferiority in the study was 1.57, thus the findings demonstrated noninferiority of deferiprone, Dr. Kwiatkowski said.

Deferiprone also showed noninferiority for the secondary endpoints of change in cardiac iron (about –0.02 ms on T2* MRI, log-transformed for both groups) and serum ferritin levels (–415 vs. –750 mcg/L for deferiprone vs. deferoxamine) at 12 months. The difference between the groups was not statistically significant for either endpoint.

Study participants, who had a mean age of 16.9 years, were aged 2 years and older with LIC between 7 and 30 mg/g dw. They were recruited from 33 sites in nine countries and randomized 2:1 to receive deferiprone or deferoxamine for up to 12 months; in patients with lower transfusional iron input and/or less severe iron load, deferiprone was dosed at 75 mg/kg daily and deferoxamine was dosed at 20 mg/kg for children and 40 mg/kg for adults. In those with higher iron input and/or more severe iron load, the deferiprone dose was 99 mg/kg daily and the deferoxamine doses were up to 40 mg/kg in children and up to 50 mg/kg for adults.

“Over the course of the treatment period, the dosage could be adjusted downward if there were side effects, or upward if there was no improvement in iron burden,” Dr Kwiatkowski said, adding that after 12 months, patients had the option of continuing on to a 2-year extension trial in which everyone received deferiprone.

No significant demographic differences were noted between the groups; 84% in both groups had sickle cell disease, and the remaining patients had other, rarer forms of transfusion-dependent anemia. Baseline iron burden was similar in the groups.

The rates of acceptable compliance over the course of the study were also similar at 69% and 79% in the deferiprone and deferoxamine arms, respectively, she noted.

No statistically significant difference between the groups was seen in the overall rate of adverse events, treatment-related AEs, serious AEs, or withdrawals from the study due to AEs. Agranulocytosis occurred in one deferiprone patient and zero deferoxamine patients, and mild or moderate neutropenia occurred in four patients and one patient in the groups, respectively.

All episodes resolved, no difference was seen in the rates of any of the serious AEs, and no unexpected serious adverse events occurred, she said.

Patients with sickle cell disease or other rare anemias whose care includes chronic blood transfusions require iron chelation to prevent iron overload. Currently, only deferoxamine and deferasirox are approved chelators in these patient populations, she said, noting that in 2011 deferiprone received accelerated Food and Drug Administration approval for the treatment of thalassemia.

The current study was conducted because of an FDA requirement for postmarket assessment of deferiprone’s efficacy and safety in patients with sickle cell disease and other anemias who develop transfusional iron overload. It was initiated prior to the approval of deferasirox for the first-line treatment of SCD, therefore it was compared only with deferoxamine, she explained.

Dr. Kwiatkowski reported research funding from Apopharma, bluebird bio, Novartis, and Terumo, and consultancy for Agios, bluebird bio, Celgene, and Imara.

sworcester@mdedge.com

ORLANDO – The oral iron chelator deferiprone showed noninferiority to deferoxamine for treating iron overload in patients with sickle cell disease and other rare anemias in a randomized open-label trial.

The least squares mean change from baseline in liver iron concentration (LIC) – the primary study endpoint – was –4.04 mg/g dry weight (dw) in 152 patients randomized to receive deferiprone, and –4.45 mg/g dw in 76 who received deferoxamine, Janet L. Kwiatkowski, MD, of the Children’s Hospital of Philadelphia reported at the annual meeting of the American Society of Hematology.

The upper limit of the stringent 96.01% confidence interval used for the evaluation of noninferiority in the study was 1.57, thus the findings demonstrated noninferiority of deferiprone, Dr. Kwiatkowski said.

Deferiprone also showed noninferiority for the secondary endpoints of change in cardiac iron (about –0.02 ms on T2* MRI, log-transformed for both groups) and serum ferritin levels (–415 vs. –750 mcg/L for deferiprone vs. deferoxamine) at 12 months. The difference between the groups was not statistically significant for either endpoint.

Study participants, who had a mean age of 16.9 years, were aged 2 years and older with LIC between 7 and 30 mg/g dw. They were recruited from 33 sites in nine countries and randomized 2:1 to receive deferiprone or deferoxamine for up to 12 months; in patients with lower transfusional iron input and/or less severe iron load, deferiprone was dosed at 75 mg/kg daily and deferoxamine was dosed at 20 mg/kg for children and 40 mg/kg for adults. In those with higher iron input and/or more severe iron load, the deferiprone dose was 99 mg/kg daily and the deferoxamine doses were up to 40 mg/kg in children and up to 50 mg/kg for adults.

“Over the course of the treatment period, the dosage could be adjusted downward if there were side effects, or upward if there was no improvement in iron burden,” Dr Kwiatkowski said, adding that after 12 months, patients had the option of continuing on to a 2-year extension trial in which everyone received deferiprone.

No significant demographic differences were noted between the groups; 84% in both groups had sickle cell disease, and the remaining patients had other, rarer forms of transfusion-dependent anemia. Baseline iron burden was similar in the groups.

The rates of acceptable compliance over the course of the study were also similar at 69% and 79% in the deferiprone and deferoxamine arms, respectively, she noted.

No statistically significant difference between the groups was seen in the overall rate of adverse events, treatment-related AEs, serious AEs, or withdrawals from the study due to AEs. Agranulocytosis occurred in one deferiprone patient and zero deferoxamine patients, and mild or moderate neutropenia occurred in four patients and one patient in the groups, respectively.

All episodes resolved, no difference was seen in the rates of any of the serious AEs, and no unexpected serious adverse events occurred, she said.

Patients with sickle cell disease or other rare anemias whose care includes chronic blood transfusions require iron chelation to prevent iron overload. Currently, only deferoxamine and deferasirox are approved chelators in these patient populations, she said, noting that in 2011 deferiprone received accelerated Food and Drug Administration approval for the treatment of thalassemia.

The current study was conducted because of an FDA requirement for postmarket assessment of deferiprone’s efficacy and safety in patients with sickle cell disease and other anemias who develop transfusional iron overload. It was initiated prior to the approval of deferasirox for the first-line treatment of SCD, therefore it was compared only with deferoxamine, she explained.

Dr. Kwiatkowski reported research funding from Apopharma, bluebird bio, Novartis, and Terumo, and consultancy for Agios, bluebird bio, Celgene, and Imara.

sworcester@mdedge.com

Assessing appendicitis in children with initial ultrasound followed by computed tomography in the absence of appendix visualization and presence of secondary signs was the most cost-effective approach, according to data from a modeling study of 10 strategies.

Ultrasound is safer and less expensive than computed tomography and avoids radiation exposure; however, cost-effectiveness models of various approaches to imaging have not been well studied, wrote Rebecca Jennings, MD, of Seattle Children’s Hospital, Washington, and colleagues.

In a study published in Pediatrics, the researchers simulated a hypothetical patient population using a Markov cohort model and compared 10 different strategies including CT only, MRI only, and ultrasound followed by CT or MRI after ultrasounds that are negative or fail to visualize the appendix.

Overall, the most cost-effective strategy for moderate-risk patients was the use of ultrasound followed by CT or MRI if the ultrasound failed to visualize the appendix and secondary signs of inflammation were present in the right lower quadrant. The cost of this strategy was $4,815, with effectiveness of 0.99694 quality-adjusted life-years. “The most cost-effective strategy is highly dependent on a patient’s risk stratification,” the researchers noted. Based on their model, imaging was not cost effective for patients with a prevalence less than 16% or greater than 95%. However, those with appendicitis risk between 16% and 95% and no secondary signs of inflammation can forgo further imaging, even without visualization of the appendix for maximum cost-effectiveness, the researchers said.

The study was limited by several factors, including the inability to account for all potential costs related to imaging and outcomes, lack of accounting for the use of sedation when assessing costs, and inability to separate imaging costs from total hospital costs, the researchers noted. However, the results suggest that tailored imaging approaches based on patient risk are the most cost-effective strategies to assess appendicitis, they said.

“The diagnosis and exclusion of appendicitis continues to be one of the primary concerns of providers who care for children with abdominal pain,” wrote Rebecca M. Rentea, MD, and Charles L. Snyder, MD, of Children’s Mercy Hospital Kansas City, Mo., in an accompanying editorial (Pediatrics. 2020 Feb;145:e20193349).

“The best diagnostic and imaging approach to appendicitis has been a topic of interest for some time, and improvements such as appendicitis scoring systems, decreased use of ionized radiation, and adoption of clinical algorithms have been incremental but steady,” they said. Despite the potential of missed appendicitis, the use of an algorithm based on an initial ultrasound and previous possibility of appendicitis described in the study was the most cost effective, they said. In addition, “the ability to visualize the appendix did not alter the most cost-effective approach in those with a moderate risk of appendicitis (most patients),” they concluded.

The study was supported by the University of Washington and Seattle Children’s Hospital Quality Improvement Scholars Program. The researchers had no financial conflicts to disclose.

Dr. Rentea and Dr. Snyder had no financial conflicts to disclose.

SOURCE: Jennings R et al. Pediatrics. 2020. doi: 10.1542/peds.2019-1352.

Assessing appendicitis in children with initial ultrasound followed by computed tomography in the absence of appendix visualization and presence of secondary signs was the most cost-effective approach, according to data from a modeling study of 10 strategies.

Ultrasound is safer and less expensive than computed tomography and avoids radiation exposure; however, cost-effectiveness models of various approaches to imaging have not been well studied, wrote Rebecca Jennings, MD, of Seattle Children’s Hospital, Washington, and colleagues.

In a study published in Pediatrics, the researchers simulated a hypothetical patient population using a Markov cohort model and compared 10 different strategies including CT only, MRI only, and ultrasound followed by CT or MRI after ultrasounds that are negative or fail to visualize the appendix.

Overall, the most cost-effective strategy for moderate-risk patients was the use of ultrasound followed by CT or MRI if the ultrasound failed to visualize the appendix and secondary signs of inflammation were present in the right lower quadrant. The cost of this strategy was $4,815, with effectiveness of 0.99694 quality-adjusted life-years. “The most cost-effective strategy is highly dependent on a patient’s risk stratification,” the researchers noted. Based on their model, imaging was not cost effective for patients with a prevalence less than 16% or greater than 95%. However, those with appendicitis risk between 16% and 95% and no secondary signs of inflammation can forgo further imaging, even without visualization of the appendix for maximum cost-effectiveness, the researchers said.

The study was limited by several factors, including the inability to account for all potential costs related to imaging and outcomes, lack of accounting for the use of sedation when assessing costs, and inability to separate imaging costs from total hospital costs, the researchers noted. However, the results suggest that tailored imaging approaches based on patient risk are the most cost-effective strategies to assess appendicitis, they said.

“The diagnosis and exclusion of appendicitis continues to be one of the primary concerns of providers who care for children with abdominal pain,” wrote Rebecca M. Rentea, MD, and Charles L. Snyder, MD, of Children’s Mercy Hospital Kansas City, Mo., in an accompanying editorial (Pediatrics. 2020 Feb;145:e20193349).

“The best diagnostic and imaging approach to appendicitis has been a topic of interest for some time, and improvements such as appendicitis scoring systems, decreased use of ionized radiation, and adoption of clinical algorithms have been incremental but steady,” they said. Despite the potential of missed appendicitis, the use of an algorithm based on an initial ultrasound and previous possibility of appendicitis described in the study was the most cost effective, they said. In addition, “the ability to visualize the appendix did not alter the most cost-effective approach in those with a moderate risk of appendicitis (most patients),” they concluded.

The study was supported by the University of Washington and Seattle Children’s Hospital Quality Improvement Scholars Program. The researchers had no financial conflicts to disclose.

Dr. Rentea and Dr. Snyder had no financial conflicts to disclose.

SOURCE: Jennings R et al. Pediatrics. 2020. doi: 10.1542/peds.2019-1352.

Assessing appendicitis in children with initial ultrasound followed by computed tomography in the absence of appendix visualization and presence of secondary signs was the most cost-effective approach, according to data from a modeling study of 10 strategies.

Ultrasound is safer and less expensive than computed tomography and avoids radiation exposure; however, cost-effectiveness models of various approaches to imaging have not been well studied, wrote Rebecca Jennings, MD, of Seattle Children’s Hospital, Washington, and colleagues.

In a study published in Pediatrics, the researchers simulated a hypothetical patient population using a Markov cohort model and compared 10 different strategies including CT only, MRI only, and ultrasound followed by CT or MRI after ultrasounds that are negative or fail to visualize the appendix.

Overall, the most cost-effective strategy for moderate-risk patients was the use of ultrasound followed by CT or MRI if the ultrasound failed to visualize the appendix and secondary signs of inflammation were present in the right lower quadrant. The cost of this strategy was $4,815, with effectiveness of 0.99694 quality-adjusted life-years. “The most cost-effective strategy is highly dependent on a patient’s risk stratification,” the researchers noted. Based on their model, imaging was not cost effective for patients with a prevalence less than 16% or greater than 95%. However, those with appendicitis risk between 16% and 95% and no secondary signs of inflammation can forgo further imaging, even without visualization of the appendix for maximum cost-effectiveness, the researchers said.

The study was limited by several factors, including the inability to account for all potential costs related to imaging and outcomes, lack of accounting for the use of sedation when assessing costs, and inability to separate imaging costs from total hospital costs, the researchers noted. However, the results suggest that tailored imaging approaches based on patient risk are the most cost-effective strategies to assess appendicitis, they said.

“The diagnosis and exclusion of appendicitis continues to be one of the primary concerns of providers who care for children with abdominal pain,” wrote Rebecca M. Rentea, MD, and Charles L. Snyder, MD, of Children’s Mercy Hospital Kansas City, Mo., in an accompanying editorial (Pediatrics. 2020 Feb;145:e20193349).

“The best diagnostic and imaging approach to appendicitis has been a topic of interest for some time, and improvements such as appendicitis scoring systems, decreased use of ionized radiation, and adoption of clinical algorithms have been incremental but steady,” they said. Despite the potential of missed appendicitis, the use of an algorithm based on an initial ultrasound and previous possibility of appendicitis described in the study was the most cost effective, they said. In addition, “the ability to visualize the appendix did not alter the most cost-effective approach in those with a moderate risk of appendicitis (most patients),” they concluded.

The study was supported by the University of Washington and Seattle Children’s Hospital Quality Improvement Scholars Program. The researchers had no financial conflicts to disclose.

Dr. Rentea and Dr. Snyder had no financial conflicts to disclose.

SOURCE: Jennings R et al. Pediatrics. 2020. doi: 10.1542/peds.2019-1352.

Newly discovered gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may improve understanding of clinical resistance mechanisms underlying the disease, according to recent research.

“We investigated patients with progressive CLL on venetoclax harboring subclonal BCL2 Gly101Val mutations for the presence of additional acquired BCL2 resistance mutations,” wrote Piers Blombery, MBBS, of the University of Melbourne in Victoria, Australia, and his colleagues in Blood.

Among 67 patients with relapsed disease treated with the BCL2 inhibitor venetoclax, the researchers identified a total of 11 patients with co-occurring BCL2 Gly101Val mutations. Each patient was enrolled in an early phase clinical trial at an institution in Australia.

With respect to testing methods, next-generation sequencing (NGS) and hybridization-based target enrichment technologies were used to detect novel acquired mutations in the BCL2 coding region.

Among those harboring the Gly101Val mutation, additional BCL2 mutations were identified in 10 patients (91%), with a median of three mutations detected per patient (range, 1-7). Previously undescribed mutations included an in-frame insertion mutation (Arg107_Arg110dup), and other substitutions (Asp103/Val156) in the BCL2 gene.

“As with the Gly101Val, these observations support the specificity of these mutations for the context of venetoclax resistance,” they wrote.

The investigators further explained that the BCL2 Asp103Glu mutation could have particular significance in the context of venetoclax sensitivity because of selective targeting of the BCL2 gene.

In comparison to wild-type aspartic acid, the BCL2 Asp103Glu substitution was linked to an approximate 20-fold reduction in affinity for venetoclax, they reported.

“[Our findings] consolidate the paradigm emerging across hematological malignancies of multiple independent molecular mechanisms underpinning an ‘oligoclonal’ pattern of clinical relapse on targeted therapies,” they concluded.

Further studies are needed to fully characterize the relationship between acquired BCL2 mutations and venetoclax resistance.

The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.

Newly discovered gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may improve understanding of clinical resistance mechanisms underlying the disease, according to recent research.

“We investigated patients with progressive CLL on venetoclax harboring subclonal BCL2 Gly101Val mutations for the presence of additional acquired BCL2 resistance mutations,” wrote Piers Blombery, MBBS, of the University of Melbourne in Victoria, Australia, and his colleagues in Blood.

Among 67 patients with relapsed disease treated with the BCL2 inhibitor venetoclax, the researchers identified a total of 11 patients with co-occurring BCL2 Gly101Val mutations. Each patient was enrolled in an early phase clinical trial at an institution in Australia.

With respect to testing methods, next-generation sequencing (NGS) and hybridization-based target enrichment technologies were used to detect novel acquired mutations in the BCL2 coding region.

Among those harboring the Gly101Val mutation, additional BCL2 mutations were identified in 10 patients (91%), with a median of three mutations detected per patient (range, 1-7). Previously undescribed mutations included an in-frame insertion mutation (Arg107_Arg110dup), and other substitutions (Asp103/Val156) in the BCL2 gene.

“As with the Gly101Val, these observations support the specificity of these mutations for the context of venetoclax resistance,” they wrote.

The investigators further explained that the BCL2 Asp103Glu mutation could have particular significance in the context of venetoclax sensitivity because of selective targeting of the BCL2 gene.

In comparison to wild-type aspartic acid, the BCL2 Asp103Glu substitution was linked to an approximate 20-fold reduction in affinity for venetoclax, they reported.

“[Our findings] consolidate the paradigm emerging across hematological malignancies of multiple independent molecular mechanisms underpinning an ‘oligoclonal’ pattern of clinical relapse on targeted therapies,” they concluded.

Further studies are needed to fully characterize the relationship between acquired BCL2 mutations and venetoclax resistance.

The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.

Newly discovered gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may improve understanding of clinical resistance mechanisms underlying the disease, according to recent research.

“We investigated patients with progressive CLL on venetoclax harboring subclonal BCL2 Gly101Val mutations for the presence of additional acquired BCL2 resistance mutations,” wrote Piers Blombery, MBBS, of the University of Melbourne in Victoria, Australia, and his colleagues in Blood.

Among 67 patients with relapsed disease treated with the BCL2 inhibitor venetoclax, the researchers identified a total of 11 patients with co-occurring BCL2 Gly101Val mutations. Each patient was enrolled in an early phase clinical trial at an institution in Australia.

With respect to testing methods, next-generation sequencing (NGS) and hybridization-based target enrichment technologies were used to detect novel acquired mutations in the BCL2 coding region.

Among those harboring the Gly101Val mutation, additional BCL2 mutations were identified in 10 patients (91%), with a median of three mutations detected per patient (range, 1-7). Previously undescribed mutations included an in-frame insertion mutation (Arg107_Arg110dup), and other substitutions (Asp103/Val156) in the BCL2 gene.

“As with the Gly101Val, these observations support the specificity of these mutations for the context of venetoclax resistance,” they wrote.

The investigators further explained that the BCL2 Asp103Glu mutation could have particular significance in the context of venetoclax sensitivity because of selective targeting of the BCL2 gene.

In comparison to wild-type aspartic acid, the BCL2 Asp103Glu substitution was linked to an approximate 20-fold reduction in affinity for venetoclax, they reported.

“[Our findings] consolidate the paradigm emerging across hematological malignancies of multiple independent molecular mechanisms underpinning an ‘oligoclonal’ pattern of clinical relapse on targeted therapies,” they concluded.

Further studies are needed to fully characterize the relationship between acquired BCL2 mutations and venetoclax resistance.

The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.

The incorporation of medical scribes into an outpatient oncology setting may lower physician burnout and improve patient care, according to a retrospective study.

“The objective of this study was to determine the effect of scribe integration on clinic workflow efficiency and physician satisfaction and quality of life in outpatient oncology clinics,” wrote Rebecca W. Gao, MD, of Stanford (Calif.) Medicine, and colleagues in the Journal of Oncology Practice.

The researchers retrospectively analyzed patient and survey data from 129 physicians connected with a tertiary care academic medical center during 2017-2019. In the study, 33 physicians were paired with a scribe, while 96 others were not.

During each patient encounter, visit duration times were recorded into an electronic medical record by a medical scribe. The scribes also performed a variety of other tasks, including collating lab results, documenting medical history, and completing postvisit summaries.

In the analysis, the team compared average visit duration times between physicians with and without a scribe. The effects of scribe integration on individual physician’s visit times were also assessed.

After analysis, the researchers found that physicians with a scribe experienced a 12.1% reduction in overall average patient visit duration, compared with visit times before scribe integration (P less than .0001). They also reported that less time was spent charting at the end of the day (P = .04).

“Compared with their peers, oncologists with scribes showed a 10%-20% decrease in the duration of all patient visits,” they explained.

With respect to patient care, survey results revealed that 90% of physicians strongly agreed they spent additional time with patients, and less time at the computer. “100% of physicians surveyed ‘strongly agreed’ that scribes improved their quality of life,” they added.

The researchers acknowledged that a key limitation of the study was the single-center design. As a result, these findings may not be applicable to physicians practicing in community-based settings.

Further studies could include financial analyses to evaluate the cost-effectiveness of medical scribe use in oncology practices, they noted.

“Our study suggests that scribes can be successfully integrated into oncology clinics and may benefit physician quality of life, clinic workflow efficiency, and the quality of physician-patient interactions,” they concluded.

The study was funded by the Stanford Cancer Center. One study author reported financial affiliations with SurgVision, Vergent Biotechnology, Novadaq Technologies, and LI-COR Biosciences.

SOURCE: Gao RW et al. J Oncol Pract. 2019 Dec 5. doi: 10.1200/JOP.19.00307.

The incorporation of medical scribes into an outpatient oncology setting may lower physician burnout and improve patient care, according to a retrospective study.

“The objective of this study was to determine the effect of scribe integration on clinic workflow efficiency and physician satisfaction and quality of life in outpatient oncology clinics,” wrote Rebecca W. Gao, MD, of Stanford (Calif.) Medicine, and colleagues in the Journal of Oncology Practice.

The researchers retrospectively analyzed patient and survey data from 129 physicians connected with a tertiary care academic medical center during 2017-2019. In the study, 33 physicians were paired with a scribe, while 96 others were not.

During each patient encounter, visit duration times were recorded into an electronic medical record by a medical scribe. The scribes also performed a variety of other tasks, including collating lab results, documenting medical history, and completing postvisit summaries.

In the analysis, the team compared average visit duration times between physicians with and without a scribe. The effects of scribe integration on individual physician’s visit times were also assessed.

After analysis, the researchers found that physicians with a scribe experienced a 12.1% reduction in overall average patient visit duration, compared with visit times before scribe integration (P less than .0001). They also reported that less time was spent charting at the end of the day (P = .04).

“Compared with their peers, oncologists with scribes showed a 10%-20% decrease in the duration of all patient visits,” they explained.

With respect to patient care, survey results revealed that 90% of physicians strongly agreed they spent additional time with patients, and less time at the computer. “100% of physicians surveyed ‘strongly agreed’ that scribes improved their quality of life,” they added.

The researchers acknowledged that a key limitation of the study was the single-center design. As a result, these findings may not be applicable to physicians practicing in community-based settings.

Further studies could include financial analyses to evaluate the cost-effectiveness of medical scribe use in oncology practices, they noted.

“Our study suggests that scribes can be successfully integrated into oncology clinics and may benefit physician quality of life, clinic workflow efficiency, and the quality of physician-patient interactions,” they concluded.

The study was funded by the Stanford Cancer Center. One study author reported financial affiliations with SurgVision, Vergent Biotechnology, Novadaq Technologies, and LI-COR Biosciences.

SOURCE: Gao RW et al. J Oncol Pract. 2019 Dec 5. doi: 10.1200/JOP.19.00307.

The incorporation of medical scribes into an outpatient oncology setting may lower physician burnout and improve patient care, according to a retrospective study.

“The objective of this study was to determine the effect of scribe integration on clinic workflow efficiency and physician satisfaction and quality of life in outpatient oncology clinics,” wrote Rebecca W. Gao, MD, of Stanford (Calif.) Medicine, and colleagues in the Journal of Oncology Practice.

The researchers retrospectively analyzed patient and survey data from 129 physicians connected with a tertiary care academic medical center during 2017-2019. In the study, 33 physicians were paired with a scribe, while 96 others were not.

During each patient encounter, visit duration times were recorded into an electronic medical record by a medical scribe. The scribes also performed a variety of other tasks, including collating lab results, documenting medical history, and completing postvisit summaries.

In the analysis, the team compared average visit duration times between physicians with and without a scribe. The effects of scribe integration on individual physician’s visit times were also assessed.

After analysis, the researchers found that physicians with a scribe experienced a 12.1% reduction in overall average patient visit duration, compared with visit times before scribe integration (P less than .0001). They also reported that less time was spent charting at the end of the day (P = .04).

“Compared with their peers, oncologists with scribes showed a 10%-20% decrease in the duration of all patient visits,” they explained.

With respect to patient care, survey results revealed that 90% of physicians strongly agreed they spent additional time with patients, and less time at the computer. “100% of physicians surveyed ‘strongly agreed’ that scribes improved their quality of life,” they added.

The researchers acknowledged that a key limitation of the study was the single-center design. As a result, these findings may not be applicable to physicians practicing in community-based settings.

Further studies could include financial analyses to evaluate the cost-effectiveness of medical scribe use in oncology practices, they noted.

“Our study suggests that scribes can be successfully integrated into oncology clinics and may benefit physician quality of life, clinic workflow efficiency, and the quality of physician-patient interactions,” they concluded.

The study was funded by the Stanford Cancer Center. One study author reported financial affiliations with SurgVision, Vergent Biotechnology, Novadaq Technologies, and LI-COR Biosciences.

SOURCE: Gao RW et al. J Oncol Pract. 2019 Dec 5. doi: 10.1200/JOP.19.00307.

LOS ANGELES – Injections may be the most common way for patients with diabetes to take insulin, but other modes of delivery are coming of age.

Doug Brunk/MDedge News

George Grunberger, MD, chairman of the Grunberger Diabetes Institute in Bloomfield Township, Mich., said that at least seven different agents that are being studied for the oral delivery of biologics for diabetes.

He outlined several at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
 

Oral insulin

ORMD-0801 from Oramed is an oral insulin capsule that prevents enzyme degradation and enhances intestinal absorption. Top-line, unpublished findings from a phase 2 study, which the company announced in November 2019, showed that ORMD-0801 significantly reduced hemoglobin A_1c levels in patients with type 2 diabetes who were inadequately controlled on other standard-of-care drugs. ORMD-0801 dosed once daily reduced HbA_1c by 0.60%, compared with 0.06% by placebo. “We’ll see when it’s going to wind up in the clinic,” Dr. Grunberger said. Oramed is also developing an oral glucagonlike peptide–1 analogue capsule, ORMD-0901, which has potential to be the first orally ingestible GLP-1 analogue.

Inhaled and absorbed insulin

Technosphere insulin (Affreza) is a novel inhalation powder for the treatment of diabetes that was developed by MannKind and approved by the Food and Drug Administration in 2014. Clinical studies have shown that Technosphere insulin delivers insulin with an ultrarapid pharmacokinetic profile that is different from all other insulin products, but similar to natural insulin release. “The idea was to develop a more patient-friendly device to deliver insulin directly into the lungs,” said Dr. Grunberger, who is also a clinical professor of internal medicine and molecular medicine and genetics at Wayne State University, Detroit. “When you inhale this into the lungs, there is one cell layer between the air sac and the circulation, so it works very quickly. The idea is to try to avoid injecting insulin to see if it helps. This is a prandial insulin – you inhale it before meals. The whole idea is that hopefully, you can reduce any fear of delayed postprandial hyperglycemia.”

In a randomized trial of 353 patients with inadequately controlled type 2 diabetes, those in the Technosphere insulin arm significantly reduced HbA_1c by 0.8% from a baseline of 8.3%, compared with the placebo arm, which was reduced by 0.4% (P less than .0001; Diabetes Care. 2015;38[12]:2274-81). A greater number of patients treated with Technosphere insulin achieved an HbA_1c of 7.0% or less, compared with placebo (38% vs. 19%; P = .0005). Dr. Grunberger noted that, in clinical trials lasting up to 2 years, patients treated with Technosphere insulin had a 40-mL greater decline from baseline in forced expiratory volume in 1 second (FEV₁ ), compared with patients treated with comparator antidiabetes treatments. “But once you stop using the drug, FEV₁ reverts to normal,” he said. “So, there does not appear to be lasting damage to your lungs and respiratory ability.”

In another development, Oral-Lyn from Generex Biotechnology, which delivers insulin through the oral mucosa, is being evaluated as a potential treatment option. In 2015, Generex partnered with the University of Toronto’s Center for Molecular Design and Preformulations to increase the bioavailability of insulin in the product and to reduce the number of sprays required to achieve effective prandial glucose control. In 2019, the company formed the NuGenerex Diabetes Research Center, which intended to accelerate the development of the reformulated Oral-Lyn-2, for type 2 diabetes, and Altsulin, for the treatment of type 1 diabetes. The programs are expected to initiate in the first quarter of 2020.

In the meantime, studies of intranasally delivered insulin continue to advance. “It works. It lowers glucose, but there is a whole slew of knowledge now about how it can also improve neurocognitive function,” Dr. Grunberger said.
 

Oral GLP-1 receptor agonists

Oral versions of glucagonlike peptide–1 (GLP-1) receptor agonists are also emerging as a treatment option. The FDA recently approved the first oral GLP-1 receptor agonist, semaglutide bound in the absorption enhancer sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). According to data from manufacturer Novo Nordisk, SNAC facilitates local increase of pH, which leads to a higher solubility. SNAC interacts with cell membranes of gastric mucosa, facilitating absorption within 30 minutes, “so the drug can penetrate the mucosa without lasting damage,” Dr. Grunberger said. The SNAC effect is size dependent and fully reversible.

In PIONEER 3, researchers found that, in adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide at dosages of 7 and 14 mg/day resulted in significantly greater reductions in HbA_1c over 26 weeks, compared with sitagliptin, but there was no significant benefit with the 3-mg/d dosage (JAMA. 2019;321[15]:1466-80). In PIONEER 4, researchers compared the efficacy and safety of oral semaglutide with subcutaneous liraglutide (Lancet. 2019;394[10192]:P39-50). “There was no difference in HbA_1c effect between the two groups, but oral semaglutide beat out sitagliptin in terms of weight loss,” Dr. Grunberger said. “It’s going to be interesting to see what’s going to happen in the marketplace as the drug gets widely launched.”
 

Nasal glucagon

He closed out his presentation by discussing the July 2019 FDA approval of Eli Lilly’s nasal glucagon for severe hypoglycemia – the first such treatment that can be administered without an injection. The nasally administered dry powder, known as Baqsimi, is a welcome alternative to current glucagon kits, “which contain multiple components,” said Dr. Grunberger, who is also a past president of the American Association of Clinical Endocrinologists. An adult pivotal study showed that supraphysiologic levels of glucagon were achieved within 5 minutes with both nasal and intramuscular glucagon (Diabetes Care. 2016;39[2]:264-70). Headache and nasal symptoms occurred more frequently with nasal glucagon, but most were resolved within 1 day. In addition, nausea and vomiting occurred at similar frequencies with nasal and intramuscular glucacon, and most cases were resolved within 1 day.

Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years, (Diabetes Care. 2016;39[4]:555-62).

Dr. Grunberger disclosed that has research contracts with Medtronic and Eli Lilly, and that he serves on speakers bureaus of Eli Lilly, Janssen, Novo Nordisk, and Sanofi.

dbrunk@mdedge.com

LOS ANGELES – Injections may be the most common way for patients with diabetes to take insulin, but other modes of delivery are coming of age.

Doug Brunk/MDedge News

George Grunberger, MD, chairman of the Grunberger Diabetes Institute in Bloomfield Township, Mich., said that at least seven different agents that are being studied for the oral delivery of biologics for diabetes.

He outlined several at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
 

Oral insulin

ORMD-0801 from Oramed is an oral insulin capsule that prevents enzyme degradation and enhances intestinal absorption. Top-line, unpublished findings from a phase 2 study, which the company announced in November 2019, showed that ORMD-0801 significantly reduced hemoglobin A_1c levels in patients with type 2 diabetes who were inadequately controlled on other standard-of-care drugs. ORMD-0801 dosed once daily reduced HbA_1c by 0.60%, compared with 0.06% by placebo. “We’ll see when it’s going to wind up in the clinic,” Dr. Grunberger said. Oramed is also developing an oral glucagonlike peptide–1 analogue capsule, ORMD-0901, which has potential to be the first orally ingestible GLP-1 analogue.

Inhaled and absorbed insulin

Technosphere insulin (Affreza) is a novel inhalation powder for the treatment of diabetes that was developed by MannKind and approved by the Food and Drug Administration in 2014. Clinical studies have shown that Technosphere insulin delivers insulin with an ultrarapid pharmacokinetic profile that is different from all other insulin products, but similar to natural insulin release. “The idea was to develop a more patient-friendly device to deliver insulin directly into the lungs,” said Dr. Grunberger, who is also a clinical professor of internal medicine and molecular medicine and genetics at Wayne State University, Detroit. “When you inhale this into the lungs, there is one cell layer between the air sac and the circulation, so it works very quickly. The idea is to try to avoid injecting insulin to see if it helps. This is a prandial insulin – you inhale it before meals. The whole idea is that hopefully, you can reduce any fear of delayed postprandial hyperglycemia.”

In a randomized trial of 353 patients with inadequately controlled type 2 diabetes, those in the Technosphere insulin arm significantly reduced HbA_1c by 0.8% from a baseline of 8.3%, compared with the placebo arm, which was reduced by 0.4% (P less than .0001; Diabetes Care. 2015;38[12]:2274-81). A greater number of patients treated with Technosphere insulin achieved an HbA_1c of 7.0% or less, compared with placebo (38% vs. 19%; P = .0005). Dr. Grunberger noted that, in clinical trials lasting up to 2 years, patients treated with Technosphere insulin had a 40-mL greater decline from baseline in forced expiratory volume in 1 second (FEV₁ ), compared with patients treated with comparator antidiabetes treatments. “But once you stop using the drug, FEV₁ reverts to normal,” he said. “So, there does not appear to be lasting damage to your lungs and respiratory ability.”

In another development, Oral-Lyn from Generex Biotechnology, which delivers insulin through the oral mucosa, is being evaluated as a potential treatment option. In 2015, Generex partnered with the University of Toronto’s Center for Molecular Design and Preformulations to increase the bioavailability of insulin in the product and to reduce the number of sprays required to achieve effective prandial glucose control. In 2019, the company formed the NuGenerex Diabetes Research Center, which intended to accelerate the development of the reformulated Oral-Lyn-2, for type 2 diabetes, and Altsulin, for the treatment of type 1 diabetes. The programs are expected to initiate in the first quarter of 2020.

In the meantime, studies of intranasally delivered insulin continue to advance. “It works. It lowers glucose, but there is a whole slew of knowledge now about how it can also improve neurocognitive function,” Dr. Grunberger said.
 

Oral GLP-1 receptor agonists

Oral versions of glucagonlike peptide–1 (GLP-1) receptor agonists are also emerging as a treatment option. The FDA recently approved the first oral GLP-1 receptor agonist, semaglutide bound in the absorption enhancer sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). According to data from manufacturer Novo Nordisk, SNAC facilitates local increase of pH, which leads to a higher solubility. SNAC interacts with cell membranes of gastric mucosa, facilitating absorption within 30 minutes, “so the drug can penetrate the mucosa without lasting damage,” Dr. Grunberger said. The SNAC effect is size dependent and fully reversible.

In PIONEER 3, researchers found that, in adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide at dosages of 7 and 14 mg/day resulted in significantly greater reductions in HbA_1c over 26 weeks, compared with sitagliptin, but there was no significant benefit with the 3-mg/d dosage (JAMA. 2019;321[15]:1466-80). In PIONEER 4, researchers compared the efficacy and safety of oral semaglutide with subcutaneous liraglutide (Lancet. 2019;394[10192]:P39-50). “There was no difference in HbA_1c effect between the two groups, but oral semaglutide beat out sitagliptin in terms of weight loss,” Dr. Grunberger said. “It’s going to be interesting to see what’s going to happen in the marketplace as the drug gets widely launched.”
 

Nasal glucagon

He closed out his presentation by discussing the July 2019 FDA approval of Eli Lilly’s nasal glucagon for severe hypoglycemia – the first such treatment that can be administered without an injection. The nasally administered dry powder, known as Baqsimi, is a welcome alternative to current glucagon kits, “which contain multiple components,” said Dr. Grunberger, who is also a past president of the American Association of Clinical Endocrinologists. An adult pivotal study showed that supraphysiologic levels of glucagon were achieved within 5 minutes with both nasal and intramuscular glucagon (Diabetes Care. 2016;39[2]:264-70). Headache and nasal symptoms occurred more frequently with nasal glucagon, but most were resolved within 1 day. In addition, nausea and vomiting occurred at similar frequencies with nasal and intramuscular glucacon, and most cases were resolved within 1 day.

Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years, (Diabetes Care. 2016;39[4]:555-62).

Dr. Grunberger disclosed that has research contracts with Medtronic and Eli Lilly, and that he serves on speakers bureaus of Eli Lilly, Janssen, Novo Nordisk, and Sanofi.

dbrunk@mdedge.com

LOS ANGELES – Injections may be the most common way for patients with diabetes to take insulin, but other modes of delivery are coming of age.

Doug Brunk/MDedge News

George Grunberger, MD, chairman of the Grunberger Diabetes Institute in Bloomfield Township, Mich., said that at least seven different agents that are being studied for the oral delivery of biologics for diabetes.

He outlined several at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
 

Oral insulin

ORMD-0801 from Oramed is an oral insulin capsule that prevents enzyme degradation and enhances intestinal absorption. Top-line, unpublished findings from a phase 2 study, which the company announced in November 2019, showed that ORMD-0801 significantly reduced hemoglobin A_1c levels in patients with type 2 diabetes who were inadequately controlled on other standard-of-care drugs. ORMD-0801 dosed once daily reduced HbA_1c by 0.60%, compared with 0.06% by placebo. “We’ll see when it’s going to wind up in the clinic,” Dr. Grunberger said. Oramed is also developing an oral glucagonlike peptide–1 analogue capsule, ORMD-0901, which has potential to be the first orally ingestible GLP-1 analogue.

Inhaled and absorbed insulin

Technosphere insulin (Affreza) is a novel inhalation powder for the treatment of diabetes that was developed by MannKind and approved by the Food and Drug Administration in 2014. Clinical studies have shown that Technosphere insulin delivers insulin with an ultrarapid pharmacokinetic profile that is different from all other insulin products, but similar to natural insulin release. “The idea was to develop a more patient-friendly device to deliver insulin directly into the lungs,” said Dr. Grunberger, who is also a clinical professor of internal medicine and molecular medicine and genetics at Wayne State University, Detroit. “When you inhale this into the lungs, there is one cell layer between the air sac and the circulation, so it works very quickly. The idea is to try to avoid injecting insulin to see if it helps. This is a prandial insulin – you inhale it before meals. The whole idea is that hopefully, you can reduce any fear of delayed postprandial hyperglycemia.”

In a randomized trial of 353 patients with inadequately controlled type 2 diabetes, those in the Technosphere insulin arm significantly reduced HbA_1c by 0.8% from a baseline of 8.3%, compared with the placebo arm, which was reduced by 0.4% (P less than .0001; Diabetes Care. 2015;38[12]:2274-81). A greater number of patients treated with Technosphere insulin achieved an HbA_1c of 7.0% or less, compared with placebo (38% vs. 19%; P = .0005). Dr. Grunberger noted that, in clinical trials lasting up to 2 years, patients treated with Technosphere insulin had a 40-mL greater decline from baseline in forced expiratory volume in 1 second (FEV₁ ), compared with patients treated with comparator antidiabetes treatments. “But once you stop using the drug, FEV₁ reverts to normal,” he said. “So, there does not appear to be lasting damage to your lungs and respiratory ability.”

In another development, Oral-Lyn from Generex Biotechnology, which delivers insulin through the oral mucosa, is being evaluated as a potential treatment option. In 2015, Generex partnered with the University of Toronto’s Center for Molecular Design and Preformulations to increase the bioavailability of insulin in the product and to reduce the number of sprays required to achieve effective prandial glucose control. In 2019, the company formed the NuGenerex Diabetes Research Center, which intended to accelerate the development of the reformulated Oral-Lyn-2, for type 2 diabetes, and Altsulin, for the treatment of type 1 diabetes. The programs are expected to initiate in the first quarter of 2020.

In the meantime, studies of intranasally delivered insulin continue to advance. “It works. It lowers glucose, but there is a whole slew of knowledge now about how it can also improve neurocognitive function,” Dr. Grunberger said.
 

Oral GLP-1 receptor agonists

Oral versions of glucagonlike peptide–1 (GLP-1) receptor agonists are also emerging as a treatment option. The FDA recently approved the first oral GLP-1 receptor agonist, semaglutide bound in the absorption enhancer sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). According to data from manufacturer Novo Nordisk, SNAC facilitates local increase of pH, which leads to a higher solubility. SNAC interacts with cell membranes of gastric mucosa, facilitating absorption within 30 minutes, “so the drug can penetrate the mucosa without lasting damage,” Dr. Grunberger said. The SNAC effect is size dependent and fully reversible.

In PIONEER 3, researchers found that, in adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide at dosages of 7 and 14 mg/day resulted in significantly greater reductions in HbA_1c over 26 weeks, compared with sitagliptin, but there was no significant benefit with the 3-mg/d dosage (JAMA. 2019;321[15]:1466-80). In PIONEER 4, researchers compared the efficacy and safety of oral semaglutide with subcutaneous liraglutide (Lancet. 2019;394[10192]:P39-50). “There was no difference in HbA_1c effect between the two groups, but oral semaglutide beat out sitagliptin in terms of weight loss,” Dr. Grunberger said. “It’s going to be interesting to see what’s going to happen in the marketplace as the drug gets widely launched.”
 

Nasal glucagon

He closed out his presentation by discussing the July 2019 FDA approval of Eli Lilly’s nasal glucagon for severe hypoglycemia – the first such treatment that can be administered without an injection. The nasally administered dry powder, known as Baqsimi, is a welcome alternative to current glucagon kits, “which contain multiple components,” said Dr. Grunberger, who is also a past president of the American Association of Clinical Endocrinologists. An adult pivotal study showed that supraphysiologic levels of glucagon were achieved within 5 minutes with both nasal and intramuscular glucagon (Diabetes Care. 2016;39[2]:264-70). Headache and nasal symptoms occurred more frequently with nasal glucagon, but most were resolved within 1 day. In addition, nausea and vomiting occurred at similar frequencies with nasal and intramuscular glucacon, and most cases were resolved within 1 day.

Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years, (Diabetes Care. 2016;39[4]:555-62).

Dr. Grunberger disclosed that has research contracts with Medtronic and Eli Lilly, and that he serves on speakers bureaus of Eli Lilly, Janssen, Novo Nordisk, and Sanofi.

dbrunk@mdedge.com

The U.S. Food and Drug Administration’s approval of an expanded indication for a leadless pacemaker for patients “who may benefit from maintenance of atrioventricular synchrony” will make this technology potentially available to nearly half of the Americans who need a pacemaker, roughly triple the number of patients who have been candidates for a leadless pacemaker up to now.

Mitchel L. Zoler/MDedge News

“This approval was huge. The complication rate with leadless pacemakers has been 63% less than the rate using pacemakers with transvenous leads,” said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication. By expanding the types of patients suitable for leadless pacing “we’ll achieve AV [atrioventricular] synchrony in more patients with fewer complications,” said Dr. Chinitz, professor of medicine and director of the Cardiac Electrophysiology and Heart Rhythm Center at NYU Langone Health in New York.

Because the device is both leadless and requires no pocket owing to its small size and placement in a patient’s right ventricle, it has implications for potentially broadening the population that could benefit from the device, he said in an interview. “When we started with this pacemaker, it was limited to elderly patients with persistent atrial fibrillation who needed only ventricular pacing, a very small group,” just under 15% of the universe of patients who need pacemakers. The broadened indication, for patients with high-grade AV block who also have atrial function, makes it possible to think of using this safer and easier-to-place device in patients who need infrequent pacing, and in patients with multiple comorbidities that give them an increased complication risk, he said. The new indication means “you’re treating a much broader patient population, doing it more safely, and creating the foundation for expanding this technology.”

The Micra AV pacemaker uses the same basic design as the previously approved Micra Transcatheter Pacing System, which came onto the U.S. market in 2016 and provides single-chamber pacing. An accelerometer on the device allows it to detect atrial motion and thereby synchronize ventricular and atrial contractions, which led to the new indication. Although the Micra AV device looks similar to the original single-chamber model, it has an entirely new circuitry that prolongs battery life during dual-chamber pacing as well as new software that incorporates the accelerometer data, explained Robert Kowal, MD, a cardiac electrophysiologist, and vice president of medical affairs and chief medical officer of cardiac rhythm and heart failure at Medtronic in Minneapolis. The battery of the Micra AV is designed to last about 15 years, Dr. Chinitz noted.

Results from two studies that Dr. Chinitz helped run established the safety and efficacy of the device for dual-chamber pacing. The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study included 64 patients who completed the study at 12 worldwide centers, which produced an average 80% AV synchrony in 33 patients with high-degree AV block (The other patients in the study had predominantly intrinsic AV conduction; Heart Rhythm. 2018 Sep;15[9]:1363-71). The MARVEL 2 study included 75 patients with either second- or third-degree AV block at 12 worldwide centers and showed that AV synchrony increased from an average of 27% without two-chamber pacing to 89% with the dual-chamber function turned on, and with 95% of patients achieving at least 70% AV synchrony (JACC Clin Electrophysiol. 2020 Jan;6[1]:94-106).

The 2016 indication for single-chamber pacing included patients with “high-grade” AV bloc with or without atrial fibrillation, typically patients for whom dual-chamber pacemaker was not a great option because of the risks for complication but with the downside of limited AV synchrony, a limitation now mitigated by the option of mechanical synchronization, Dr. Kowal said. The AV device remains intended for patients with high-grade AV node block, which means patients with second- or third-degree block, he added in an interview. The estimated prevalence of third-degree AV block among U.S. adults is about 0.02%, which translates into about 50,000 people; the estimated prevalence of second-degree AV block is much less, about 10% of the third-degree prevalence.

Despite the substantial cut in complications by a leadless and pocketless pacemaker, “some patients may still benefit from a traditional dual-chamber pacemaker,” specifically active patients who might sometimes get their heart rates up with exercise to levels of about 150 beats/min or higher, Dr. Kowal said. That’s because currently the programing algorithms used to synchronize the ventricle and atrium become less reliable at heart rates above 105 beats/min, he explained. However, the ability for mechanical synchronization to keep up at higher heart rates should improve as additional data are collected that can refine the algorithms. It’s also unusual for most patients who are pacemaker candidates to reach heart rates this high, he said.

The MARVEL and MARVEL 2 studies were sponsored by Medtronic, the company that markets Micra pacemakers. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer, and he has also received fellowship support from Biotronik and Boston Scientific. Dr. Kowal is a Medtronic employee.

mzoler@mdedge.com

The U.S. Food and Drug Administration’s approval of an expanded indication for a leadless pacemaker for patients “who may benefit from maintenance of atrioventricular synchrony” will make this technology potentially available to nearly half of the Americans who need a pacemaker, roughly triple the number of patients who have been candidates for a leadless pacemaker up to now.

Mitchel L. Zoler/MDedge News

“This approval was huge. The complication rate with leadless pacemakers has been 63% less than the rate using pacemakers with transvenous leads,” said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication. By expanding the types of patients suitable for leadless pacing “we’ll achieve AV [atrioventricular] synchrony in more patients with fewer complications,” said Dr. Chinitz, professor of medicine and director of the Cardiac Electrophysiology and Heart Rhythm Center at NYU Langone Health in New York.

Because the device is both leadless and requires no pocket owing to its small size and placement in a patient’s right ventricle, it has implications for potentially broadening the population that could benefit from the device, he said in an interview. “When we started with this pacemaker, it was limited to elderly patients with persistent atrial fibrillation who needed only ventricular pacing, a very small group,” just under 15% of the universe of patients who need pacemakers. The broadened indication, for patients with high-grade AV block who also have atrial function, makes it possible to think of using this safer and easier-to-place device in patients who need infrequent pacing, and in patients with multiple comorbidities that give them an increased complication risk, he said. The new indication means “you’re treating a much broader patient population, doing it more safely, and creating the foundation for expanding this technology.”

The Micra AV pacemaker uses the same basic design as the previously approved Micra Transcatheter Pacing System, which came onto the U.S. market in 2016 and provides single-chamber pacing. An accelerometer on the device allows it to detect atrial motion and thereby synchronize ventricular and atrial contractions, which led to the new indication. Although the Micra AV device looks similar to the original single-chamber model, it has an entirely new circuitry that prolongs battery life during dual-chamber pacing as well as new software that incorporates the accelerometer data, explained Robert Kowal, MD, a cardiac electrophysiologist, and vice president of medical affairs and chief medical officer of cardiac rhythm and heart failure at Medtronic in Minneapolis. The battery of the Micra AV is designed to last about 15 years, Dr. Chinitz noted.

Results from two studies that Dr. Chinitz helped run established the safety and efficacy of the device for dual-chamber pacing. The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study included 64 patients who completed the study at 12 worldwide centers, which produced an average 80% AV synchrony in 33 patients with high-degree AV block (The other patients in the study had predominantly intrinsic AV conduction; Heart Rhythm. 2018 Sep;15[9]:1363-71). The MARVEL 2 study included 75 patients with either second- or third-degree AV block at 12 worldwide centers and showed that AV synchrony increased from an average of 27% without two-chamber pacing to 89% with the dual-chamber function turned on, and with 95% of patients achieving at least 70% AV synchrony (JACC Clin Electrophysiol. 2020 Jan;6[1]:94-106).

The 2016 indication for single-chamber pacing included patients with “high-grade” AV bloc with or without atrial fibrillation, typically patients for whom dual-chamber pacemaker was not a great option because of the risks for complication but with the downside of limited AV synchrony, a limitation now mitigated by the option of mechanical synchronization, Dr. Kowal said. The AV device remains intended for patients with high-grade AV node block, which means patients with second- or third-degree block, he added in an interview. The estimated prevalence of third-degree AV block among U.S. adults is about 0.02%, which translates into about 50,000 people; the estimated prevalence of second-degree AV block is much less, about 10% of the third-degree prevalence.

Despite the substantial cut in complications by a leadless and pocketless pacemaker, “some patients may still benefit from a traditional dual-chamber pacemaker,” specifically active patients who might sometimes get their heart rates up with exercise to levels of about 150 beats/min or higher, Dr. Kowal said. That’s because currently the programing algorithms used to synchronize the ventricle and atrium become less reliable at heart rates above 105 beats/min, he explained. However, the ability for mechanical synchronization to keep up at higher heart rates should improve as additional data are collected that can refine the algorithms. It’s also unusual for most patients who are pacemaker candidates to reach heart rates this high, he said.

The MARVEL and MARVEL 2 studies were sponsored by Medtronic, the company that markets Micra pacemakers. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer, and he has also received fellowship support from Biotronik and Boston Scientific. Dr. Kowal is a Medtronic employee.

mzoler@mdedge.com

The U.S. Food and Drug Administration’s approval of an expanded indication for a leadless pacemaker for patients “who may benefit from maintenance of atrioventricular synchrony” will make this technology potentially available to nearly half of the Americans who need a pacemaker, roughly triple the number of patients who have been candidates for a leadless pacemaker up to now.

Mitchel L. Zoler/MDedge News

“This approval was huge. The complication rate with leadless pacemakers has been 63% less than the rate using pacemakers with transvenous leads,” said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication. By expanding the types of patients suitable for leadless pacing “we’ll achieve AV [atrioventricular] synchrony in more patients with fewer complications,” said Dr. Chinitz, professor of medicine and director of the Cardiac Electrophysiology and Heart Rhythm Center at NYU Langone Health in New York.

Because the device is both leadless and requires no pocket owing to its small size and placement in a patient’s right ventricle, it has implications for potentially broadening the population that could benefit from the device, he said in an interview. “When we started with this pacemaker, it was limited to elderly patients with persistent atrial fibrillation who needed only ventricular pacing, a very small group,” just under 15% of the universe of patients who need pacemakers. The broadened indication, for patients with high-grade AV block who also have atrial function, makes it possible to think of using this safer and easier-to-place device in patients who need infrequent pacing, and in patients with multiple comorbidities that give them an increased complication risk, he said. The new indication means “you’re treating a much broader patient population, doing it more safely, and creating the foundation for expanding this technology.”

The Micra AV pacemaker uses the same basic design as the previously approved Micra Transcatheter Pacing System, which came onto the U.S. market in 2016 and provides single-chamber pacing. An accelerometer on the device allows it to detect atrial motion and thereby synchronize ventricular and atrial contractions, which led to the new indication. Although the Micra AV device looks similar to the original single-chamber model, it has an entirely new circuitry that prolongs battery life during dual-chamber pacing as well as new software that incorporates the accelerometer data, explained Robert Kowal, MD, a cardiac electrophysiologist, and vice president of medical affairs and chief medical officer of cardiac rhythm and heart failure at Medtronic in Minneapolis. The battery of the Micra AV is designed to last about 15 years, Dr. Chinitz noted.

Results from two studies that Dr. Chinitz helped run established the safety and efficacy of the device for dual-chamber pacing. The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study included 64 patients who completed the study at 12 worldwide centers, which produced an average 80% AV synchrony in 33 patients with high-degree AV block (The other patients in the study had predominantly intrinsic AV conduction; Heart Rhythm. 2018 Sep;15[9]:1363-71). The MARVEL 2 study included 75 patients with either second- or third-degree AV block at 12 worldwide centers and showed that AV synchrony increased from an average of 27% without two-chamber pacing to 89% with the dual-chamber function turned on, and with 95% of patients achieving at least 70% AV synchrony (JACC Clin Electrophysiol. 2020 Jan;6[1]:94-106).

The 2016 indication for single-chamber pacing included patients with “high-grade” AV bloc with or without atrial fibrillation, typically patients for whom dual-chamber pacemaker was not a great option because of the risks for complication but with the downside of limited AV synchrony, a limitation now mitigated by the option of mechanical synchronization, Dr. Kowal said. The AV device remains intended for patients with high-grade AV node block, which means patients with second- or third-degree block, he added in an interview. The estimated prevalence of third-degree AV block among U.S. adults is about 0.02%, which translates into about 50,000 people; the estimated prevalence of second-degree AV block is much less, about 10% of the third-degree prevalence.

Despite the substantial cut in complications by a leadless and pocketless pacemaker, “some patients may still benefit from a traditional dual-chamber pacemaker,” specifically active patients who might sometimes get their heart rates up with exercise to levels of about 150 beats/min or higher, Dr. Kowal said. That’s because currently the programing algorithms used to synchronize the ventricle and atrium become less reliable at heart rates above 105 beats/min, he explained. However, the ability for mechanical synchronization to keep up at higher heart rates should improve as additional data are collected that can refine the algorithms. It’s also unusual for most patients who are pacemaker candidates to reach heart rates this high, he said.

The MARVEL and MARVEL 2 studies were sponsored by Medtronic, the company that markets Micra pacemakers. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer, and he has also received fellowship support from Biotronik and Boston Scientific. Dr. Kowal is a Medtronic employee.

mzoler@mdedge.com

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) provides “robust, sustained efficacy” in patients with Hodgkin lymphoma, according to investigators.

In the ECHELON-1 trial, investigators compared A+AVD to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for stage III or IV Hodgkin lymphoma. The 3-year progression-free survival (PFS) was superior in patients who received A+AVD, and this benefit was seen across most subgroups.

David J. Straus, MD, of Memorial Sloan Kettering Cancer Center in New York and his colleagues detailed these findings in Blood.

The phase 3 trial (NCT01712490) enrolled 1,334 patients with stage III or IV classical Hodgkin lymphoma. They were randomized to receive A+AVD (n = 664) or ABVD (n = 670). Baseline characteristics were similar between the treatment arms.

Positron emission tomography status after cycle 2 (PET2) was similar between the treatment arms as well. Most patients – 89% of the A+AVD arm and 86% of the ABVD arm – were PET2 negative. Treating physicians used PET2 status as a guide to potentially switch patients to an alternative regimen (radiotherapy or chemotherapy with or without transplant).

In a prior analysis, the study’s primary endpoint was modified PFS (time to progression, death, or noncomplete response after frontline therapy) per an independent review committee (N Engl J Med. 2018;378:331-44). The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm (hazard ratio, 0.77; P = .04).

PFS update

In the current analysis, the main exploratory endpoint was PFS per investigator. The 3-year PFS rate was significantly higher in the A+AVD arm than in the ABVD arm – 83.1% and 76.0%, respectively (HR, 0.704; P = .005).

The investigators observed a “consistent improvement in PFS” in the A+AVD arm, regardless of disease stage, International Prognostic score, Eastern Cooperative Oncology Group status, sex, or age. There was a significant improvement in PFS with A+AVD in PET2-negative patients and a trend toward improvement in PET2-positive patients. In the PET2-negative patients, the 3-year PFS was 85.8% in the A+AVD arm and 79.5% in the ABVD arm (HR, 0.69; P = .009). In PET2-positive patients, the 3-year PFS was 67.7% and 51.5%, respectively (HR, 0.59; P = .077).

“These data highlight that A+AVD provides a durable efficacy benefit, compared with ABVD, for frontline stage III/IV cHL [classical Hodgkin lymphoma], which is consistent across key subgroups regardless of patient status at PET2,” Dr. Straus and his colleagues wrote.

Safety update

In both treatment arms, peripheral neuropathy continued to improve or resolve with longer follow-up. Among patients who developed peripheral neuropathy, 78% in the A+AVD arm and 83% in the ABVD arm had improvement or resolution of the condition at 3 years.

Most patients had complete resolution of peripheral neuropathy; 62% in the A+AVD arm and 73% in the ABVD arm. The median time to complete resolution was 28 weeks (range, 0-167 weeks) after stopping A+AVD and 14 weeks (range, 0-188 weeks) after stopping ABVD.

The incidence of secondary malignancies was similar between the treatment arms. There were 14 secondary malignancies in the A+AVD arm (6 solid tumors, 8 hematologic malignancies) and 20 in the ABVD arm (9 solid tumors, 11 hematologic malignancies).

“A+AVD provided a sustained PFS benefit with a predictable and manageable safety profile,” Dr. Straus and colleagues wrote. “These data further support the advantages of A+AVD versus ABVD as frontline treatment of patients with advanced stage III or IV cHL [classical Hodgkin lymphoma].”

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals (a subsidiary of Takeda) and Seattle Genetics. The investigators disclosed relationships with Millennium, Takeda, Seattle Genetics, and a range of other companies.

jensmith@mdedge.com

SOURCE: Straus DJ et al. Blood. 2020 Jan 16. pii: blood.2019003127. doi: 10.1182/blood.2019003127.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) provides “robust, sustained efficacy” in patients with Hodgkin lymphoma, according to investigators.

In the ECHELON-1 trial, investigators compared A+AVD to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for stage III or IV Hodgkin lymphoma. The 3-year progression-free survival (PFS) was superior in patients who received A+AVD, and this benefit was seen across most subgroups.

David J. Straus, MD, of Memorial Sloan Kettering Cancer Center in New York and his colleagues detailed these findings in Blood.

The phase 3 trial (NCT01712490) enrolled 1,334 patients with stage III or IV classical Hodgkin lymphoma. They were randomized to receive A+AVD (n = 664) or ABVD (n = 670). Baseline characteristics were similar between the treatment arms.

Positron emission tomography status after cycle 2 (PET2) was similar between the treatment arms as well. Most patients – 89% of the A+AVD arm and 86% of the ABVD arm – were PET2 negative. Treating physicians used PET2 status as a guide to potentially switch patients to an alternative regimen (radiotherapy or chemotherapy with or without transplant).

In a prior analysis, the study’s primary endpoint was modified PFS (time to progression, death, or noncomplete response after frontline therapy) per an independent review committee (N Engl J Med. 2018;378:331-44). The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm (hazard ratio, 0.77; P = .04).

PFS update

In the current analysis, the main exploratory endpoint was PFS per investigator. The 3-year PFS rate was significantly higher in the A+AVD arm than in the ABVD arm – 83.1% and 76.0%, respectively (HR, 0.704; P = .005).

The investigators observed a “consistent improvement in PFS” in the A+AVD arm, regardless of disease stage, International Prognostic score, Eastern Cooperative Oncology Group status, sex, or age. There was a significant improvement in PFS with A+AVD in PET2-negative patients and a trend toward improvement in PET2-positive patients. In the PET2-negative patients, the 3-year PFS was 85.8% in the A+AVD arm and 79.5% in the ABVD arm (HR, 0.69; P = .009). In PET2-positive patients, the 3-year PFS was 67.7% and 51.5%, respectively (HR, 0.59; P = .077).

“These data highlight that A+AVD provides a durable efficacy benefit, compared with ABVD, for frontline stage III/IV cHL [classical Hodgkin lymphoma], which is consistent across key subgroups regardless of patient status at PET2,” Dr. Straus and his colleagues wrote.

Safety update

In both treatment arms, peripheral neuropathy continued to improve or resolve with longer follow-up. Among patients who developed peripheral neuropathy, 78% in the A+AVD arm and 83% in the ABVD arm had improvement or resolution of the condition at 3 years.

Most patients had complete resolution of peripheral neuropathy; 62% in the A+AVD arm and 73% in the ABVD arm. The median time to complete resolution was 28 weeks (range, 0-167 weeks) after stopping A+AVD and 14 weeks (range, 0-188 weeks) after stopping ABVD.

The incidence of secondary malignancies was similar between the treatment arms. There were 14 secondary malignancies in the A+AVD arm (6 solid tumors, 8 hematologic malignancies) and 20 in the ABVD arm (9 solid tumors, 11 hematologic malignancies).

“A+AVD provided a sustained PFS benefit with a predictable and manageable safety profile,” Dr. Straus and colleagues wrote. “These data further support the advantages of A+AVD versus ABVD as frontline treatment of patients with advanced stage III or IV cHL [classical Hodgkin lymphoma].”

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals (a subsidiary of Takeda) and Seattle Genetics. The investigators disclosed relationships with Millennium, Takeda, Seattle Genetics, and a range of other companies.

jensmith@mdedge.com

SOURCE: Straus DJ et al. Blood. 2020 Jan 16. pii: blood.2019003127. doi: 10.1182/blood.2019003127.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) provides “robust, sustained efficacy” in patients with Hodgkin lymphoma, according to investigators.

In the ECHELON-1 trial, investigators compared A+AVD to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for stage III or IV Hodgkin lymphoma. The 3-year progression-free survival (PFS) was superior in patients who received A+AVD, and this benefit was seen across most subgroups.

David J. Straus, MD, of Memorial Sloan Kettering Cancer Center in New York and his colleagues detailed these findings in Blood.

The phase 3 trial (NCT01712490) enrolled 1,334 patients with stage III or IV classical Hodgkin lymphoma. They were randomized to receive A+AVD (n = 664) or ABVD (n = 670). Baseline characteristics were similar between the treatment arms.

Positron emission tomography status after cycle 2 (PET2) was similar between the treatment arms as well. Most patients – 89% of the A+AVD arm and 86% of the ABVD arm – were PET2 negative. Treating physicians used PET2 status as a guide to potentially switch patients to an alternative regimen (radiotherapy or chemotherapy with or without transplant).

In a prior analysis, the study’s primary endpoint was modified PFS (time to progression, death, or noncomplete response after frontline therapy) per an independent review committee (N Engl J Med. 2018;378:331-44). The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm (hazard ratio, 0.77; P = .04).

PFS update

In the current analysis, the main exploratory endpoint was PFS per investigator. The 3-year PFS rate was significantly higher in the A+AVD arm than in the ABVD arm – 83.1% and 76.0%, respectively (HR, 0.704; P = .005).

The investigators observed a “consistent improvement in PFS” in the A+AVD arm, regardless of disease stage, International Prognostic score, Eastern Cooperative Oncology Group status, sex, or age. There was a significant improvement in PFS with A+AVD in PET2-negative patients and a trend toward improvement in PET2-positive patients. In the PET2-negative patients, the 3-year PFS was 85.8% in the A+AVD arm and 79.5% in the ABVD arm (HR, 0.69; P = .009). In PET2-positive patients, the 3-year PFS was 67.7% and 51.5%, respectively (HR, 0.59; P = .077).

“These data highlight that A+AVD provides a durable efficacy benefit, compared with ABVD, for frontline stage III/IV cHL [classical Hodgkin lymphoma], which is consistent across key subgroups regardless of patient status at PET2,” Dr. Straus and his colleagues wrote.

Safety update

In both treatment arms, peripheral neuropathy continued to improve or resolve with longer follow-up. Among patients who developed peripheral neuropathy, 78% in the A+AVD arm and 83% in the ABVD arm had improvement or resolution of the condition at 3 years.

Most patients had complete resolution of peripheral neuropathy; 62% in the A+AVD arm and 73% in the ABVD arm. The median time to complete resolution was 28 weeks (range, 0-167 weeks) after stopping A+AVD and 14 weeks (range, 0-188 weeks) after stopping ABVD.

The incidence of secondary malignancies was similar between the treatment arms. There were 14 secondary malignancies in the A+AVD arm (6 solid tumors, 8 hematologic malignancies) and 20 in the ABVD arm (9 solid tumors, 11 hematologic malignancies).

“A+AVD provided a sustained PFS benefit with a predictable and manageable safety profile,” Dr. Straus and colleagues wrote. “These data further support the advantages of A+AVD versus ABVD as frontline treatment of patients with advanced stage III or IV cHL [classical Hodgkin lymphoma].”

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals (a subsidiary of Takeda) and Seattle Genetics. The investigators disclosed relationships with Millennium, Takeda, Seattle Genetics, and a range of other companies.

jensmith@mdedge.com

SOURCE: Straus DJ et al. Blood. 2020 Jan 16. pii: blood.2019003127. doi: 10.1182/blood.2019003127.

Most patients with epidermolysis bullosa who use topical products choose antimicrobials, according to data from a survey of 202 children and adults.

Management of epidermolysis bullosa (EB) involves a combination of skin protection and infection management, but patient home care practices have not been well studied, wrote Leila Shayegan of Columbia University, New York, and colleagues.

In a study published in Pediatric Dermatology, the researchers surveyed 202 patients who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database during 2017. The patients ranged in age from 1 month to 62 years with an average age of 11 years; 52% were female. The patients represented a range of EB subtypes, including 130 patients with dystrophic EB, 51 patients with EB simplex, 21 with junctional EB, and 3 patients each with Kindler syndrome and unspecified subtypes.

Overall, most of the patients reported cleaning their skin either every day (37%) or every other day (32%). Of the 188 patients who reported using topical products on their wounds, 131 (70%) said they used at least one antimicrobial product, while 125 patients (66%) reported using at least one emollient; 32 (17%) used emollients only, and 21(11%) reported no use of topical products.

The most popular topical antibiotics were mupirocin (31%) and bacitracin (31%). In addition, 14% of respondents used silver-containing products, and 16% used medical-grade honey. Roughly half (51%) of patients who reported use of at least one antimicrobial product used two or more different antimicrobial products.

A total of 38% of patients used only water for cleansing. Of the 131 patients who reported using additives in their cleansing water, 57% added salt, 54% added bleach, 27% added vinegar, and 26% reported “other” additive use, which could include Epsom salt, baking soda, oatmeal, or essential oils, the researchers said. The concentrations of these additives ranged from barely effective 0.002% sodium hypochlorite and 0.002% acetic acid solutions to potentially cytotoxic solutions of 0.09% sodium hypochlorite and 0.156% acetic acid.

“Although the survey was not designed to correlate skin care practices with wound culture results and resistance patterns, widespread use of topical antimicrobials described among EB patients highlights the need for increased emphasis on antibiotic stewardship,” the researchers noted. They added that health care providers should educate patients and families not only about mindful use of antibiotics, but also appropriate concentrations of cleansing additives.

“Optimizing EB patient home skin care routines, along with future longitudinal studies on the impact of EB skin care interventions on microbial resistance patterns, wound healing and [squamous cell carcinoma] risk are necessary to improve outcomes for patients with EB,” they emphasized.

The Epidermolysis Bullosa Clinical Characterization and Outcomes Database used in the study is funded by the Epidermolysis Bullosa Research Partnership and the Epidermolysis Bullosa Medical Research Foundation. Ms. Shayegan had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies including Abeona Therapeutics, Castle Creek Pharmaceuticals, Fibrocell Science, ProQR, and Scioderm.

SOURCE: Shayegan L et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14102.

Most patients with epidermolysis bullosa who use topical products choose antimicrobials, according to data from a survey of 202 children and adults.

Management of epidermolysis bullosa (EB) involves a combination of skin protection and infection management, but patient home care practices have not been well studied, wrote Leila Shayegan of Columbia University, New York, and colleagues.

In a study published in Pediatric Dermatology, the researchers surveyed 202 patients who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database during 2017. The patients ranged in age from 1 month to 62 years with an average age of 11 years; 52% were female. The patients represented a range of EB subtypes, including 130 patients with dystrophic EB, 51 patients with EB simplex, 21 with junctional EB, and 3 patients each with Kindler syndrome and unspecified subtypes.

Overall, most of the patients reported cleaning their skin either every day (37%) or every other day (32%). Of the 188 patients who reported using topical products on their wounds, 131 (70%) said they used at least one antimicrobial product, while 125 patients (66%) reported using at least one emollient; 32 (17%) used emollients only, and 21(11%) reported no use of topical products.

The most popular topical antibiotics were mupirocin (31%) and bacitracin (31%). In addition, 14% of respondents used silver-containing products, and 16% used medical-grade honey. Roughly half (51%) of patients who reported use of at least one antimicrobial product used two or more different antimicrobial products.

A total of 38% of patients used only water for cleansing. Of the 131 patients who reported using additives in their cleansing water, 57% added salt, 54% added bleach, 27% added vinegar, and 26% reported “other” additive use, which could include Epsom salt, baking soda, oatmeal, or essential oils, the researchers said. The concentrations of these additives ranged from barely effective 0.002% sodium hypochlorite and 0.002% acetic acid solutions to potentially cytotoxic solutions of 0.09% sodium hypochlorite and 0.156% acetic acid.

“Although the survey was not designed to correlate skin care practices with wound culture results and resistance patterns, widespread use of topical antimicrobials described among EB patients highlights the need for increased emphasis on antibiotic stewardship,” the researchers noted. They added that health care providers should educate patients and families not only about mindful use of antibiotics, but also appropriate concentrations of cleansing additives.

“Optimizing EB patient home skin care routines, along with future longitudinal studies on the impact of EB skin care interventions on microbial resistance patterns, wound healing and [squamous cell carcinoma] risk are necessary to improve outcomes for patients with EB,” they emphasized.

The Epidermolysis Bullosa Clinical Characterization and Outcomes Database used in the study is funded by the Epidermolysis Bullosa Research Partnership and the Epidermolysis Bullosa Medical Research Foundation. Ms. Shayegan had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies including Abeona Therapeutics, Castle Creek Pharmaceuticals, Fibrocell Science, ProQR, and Scioderm.

SOURCE: Shayegan L et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14102.

Most patients with epidermolysis bullosa who use topical products choose antimicrobials, according to data from a survey of 202 children and adults.

Management of epidermolysis bullosa (EB) involves a combination of skin protection and infection management, but patient home care practices have not been well studied, wrote Leila Shayegan of Columbia University, New York, and colleagues.

In a study published in Pediatric Dermatology, the researchers surveyed 202 patients who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database during 2017. The patients ranged in age from 1 month to 62 years with an average age of 11 years; 52% were female. The patients represented a range of EB subtypes, including 130 patients with dystrophic EB, 51 patients with EB simplex, 21 with junctional EB, and 3 patients each with Kindler syndrome and unspecified subtypes.

Overall, most of the patients reported cleaning their skin either every day (37%) or every other day (32%). Of the 188 patients who reported using topical products on their wounds, 131 (70%) said they used at least one antimicrobial product, while 125 patients (66%) reported using at least one emollient; 32 (17%) used emollients only, and 21(11%) reported no use of topical products.

The most popular topical antibiotics were mupirocin (31%) and bacitracin (31%). In addition, 14% of respondents used silver-containing products, and 16% used medical-grade honey. Roughly half (51%) of patients who reported use of at least one antimicrobial product used two or more different antimicrobial products.

A total of 38% of patients used only water for cleansing. Of the 131 patients who reported using additives in their cleansing water, 57% added salt, 54% added bleach, 27% added vinegar, and 26% reported “other” additive use, which could include Epsom salt, baking soda, oatmeal, or essential oils, the researchers said. The concentrations of these additives ranged from barely effective 0.002% sodium hypochlorite and 0.002% acetic acid solutions to potentially cytotoxic solutions of 0.09% sodium hypochlorite and 0.156% acetic acid.

“Although the survey was not designed to correlate skin care practices with wound culture results and resistance patterns, widespread use of topical antimicrobials described among EB patients highlights the need for increased emphasis on antibiotic stewardship,” the researchers noted. They added that health care providers should educate patients and families not only about mindful use of antibiotics, but also appropriate concentrations of cleansing additives.

“Optimizing EB patient home skin care routines, along with future longitudinal studies on the impact of EB skin care interventions on microbial resistance patterns, wound healing and [squamous cell carcinoma] risk are necessary to improve outcomes for patients with EB,” they emphasized.

The Epidermolysis Bullosa Clinical Characterization and Outcomes Database used in the study is funded by the Epidermolysis Bullosa Research Partnership and the Epidermolysis Bullosa Medical Research Foundation. Ms. Shayegan had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies including Abeona Therapeutics, Castle Creek Pharmaceuticals, Fibrocell Science, ProQR, and Scioderm.

SOURCE: Shayegan L et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14102.

Enrichment next-generation sequencing (NGS) provides a more cost-efficient and sensitive method for detecting and sequencing novel coronaviruses from wild bat populations, according to a study reported in mSphere, an open-access journal from the American Society for Microbiology.

Wikimedia Commons/Mickey Samuni-Blank

With the appearance of the new zoonotic Wuhan coronavirus, the importance of monitoring the likelihood of new virus risks in wildlife reservoirs has been heightened. Bats in particular have been found to be the most common reservoir of coronaviruses, including being a probable source or mixing vessel for two previous modern epidemic coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

“We should be alert and vigilant with the knowledge that bat CoVs [coronaviruses] are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to Bei Li, MD, of the Wuhan (China) Institute of Virology, and colleagues.

“We previously provided serological evidence that [HKU8-related] CoV had jumped over from bats to camels and recombined with MERS-CoV, alerting other researchers that the CoV species could be dangerous. ... Genome-level comparison is needed to monitor the risk of alterations in species tropism and pathogenesis,” according to study authors. They performed a study to develop a more effective and cost efficient method for detecting and sequencing novel coronaviruses in the bat population.

The taxonomy of coronaviruses is particularly complex and may be too narrowly defined, given the high level of genetic plasticity found. There are four genera (Alpha-, Beta-, Gamma-, and Deltacoronavirus) consisting of 38 unique species in the CoV subfamily Orthocoronavirinae, and the number is increasing. Viral taxomists rely on the open reading frame 1b (ORF1b) gene for classification, but viruses in the same species may show great diversity in regions outside ORF1b, confounding the species designation. In particular, bat CoVs classed as the same species can differ significantly in terms of receptor usage or virus-host interaction, as observed in bat SARS-related CoVs, according to the researchers.

The researchers obtained RNA from previous bat CoV surveillance projects, which used bat rectal swabs. Libraries for NGS were constructed from total RNA and processed to generate RNA fragments larger than 300 nucleotides. Following first- and second-strand cDNA synthesis, double-stranded cDNA was purified and the library was amplified by polymerase chain reaction (PCR) technology.

Targeted CoV genome enrichment was achieved using 4,303 customized biotinylated 120-mer baits. These baits were designed from 90 representative CoV genomes, and in silico analysis determined that these baits should target the known CoV species tested. These baits were added and hybridized to the libraries. To capture virus-specific library fragments, streptavidin magnetic beads (which bind to biotin) were added to the hybridization reaction mixture. The beads were then washed to remove unbound DNA. The postcapture virus-specific library fragments were then amplified using a subsequent round of PCR.

The enrichment NGS were retrospectively complemented with unbiased NGS and/or additional Sanger sequencing to obtain full-length genomes. The study showed that enrichment NGS not only decreased the amount of data requiring analysis but produced full-length genome coverage in both laboratory and clinical samples.

Using this technology, the researchers “effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.” In addition, they noted that using standard targeted PCR, which is common practice for many surveillance studies, would not have discovered this diversity.

“We should be alert and vigilant with the knowledge that bat CoVs are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to the researchers.

“We have provided a cost-effective methodology for bat CoV surveillance. The high genetic diversity observed in our newly sequenced samples suggests further work is needed to characterize these bat CoVs prior to or in the early stages of spillover to humans,” the authors concluded.

This study was supported by the Chinese government. The authors reported that they had no conflicts.

Viral genome data for new CoVs from this study are available in GenBank under accession numbers MN611517 to MN611525.

mlesney@mdedge.com

SOURCE: Li B et al. mSphere 2020 Jan 29;5:e00807-19.

Enrichment next-generation sequencing (NGS) provides a more cost-efficient and sensitive method for detecting and sequencing novel coronaviruses from wild bat populations, according to a study reported in mSphere, an open-access journal from the American Society for Microbiology.

Wikimedia Commons/Mickey Samuni-Blank

With the appearance of the new zoonotic Wuhan coronavirus, the importance of monitoring the likelihood of new virus risks in wildlife reservoirs has been heightened. Bats in particular have been found to be the most common reservoir of coronaviruses, including being a probable source or mixing vessel for two previous modern epidemic coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

“We should be alert and vigilant with the knowledge that bat CoVs [coronaviruses] are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to Bei Li, MD, of the Wuhan (China) Institute of Virology, and colleagues.

“We previously provided serological evidence that [HKU8-related] CoV had jumped over from bats to camels and recombined with MERS-CoV, alerting other researchers that the CoV species could be dangerous. ... Genome-level comparison is needed to monitor the risk of alterations in species tropism and pathogenesis,” according to study authors. They performed a study to develop a more effective and cost efficient method for detecting and sequencing novel coronaviruses in the bat population.

The taxonomy of coronaviruses is particularly complex and may be too narrowly defined, given the high level of genetic plasticity found. There are four genera (Alpha-, Beta-, Gamma-, and Deltacoronavirus) consisting of 38 unique species in the CoV subfamily Orthocoronavirinae, and the number is increasing. Viral taxomists rely on the open reading frame 1b (ORF1b) gene for classification, but viruses in the same species may show great diversity in regions outside ORF1b, confounding the species designation. In particular, bat CoVs classed as the same species can differ significantly in terms of receptor usage or virus-host interaction, as observed in bat SARS-related CoVs, according to the researchers.

The researchers obtained RNA from previous bat CoV surveillance projects, which used bat rectal swabs. Libraries for NGS were constructed from total RNA and processed to generate RNA fragments larger than 300 nucleotides. Following first- and second-strand cDNA synthesis, double-stranded cDNA was purified and the library was amplified by polymerase chain reaction (PCR) technology.

Targeted CoV genome enrichment was achieved using 4,303 customized biotinylated 120-mer baits. These baits were designed from 90 representative CoV genomes, and in silico analysis determined that these baits should target the known CoV species tested. These baits were added and hybridized to the libraries. To capture virus-specific library fragments, streptavidin magnetic beads (which bind to biotin) were added to the hybridization reaction mixture. The beads were then washed to remove unbound DNA. The postcapture virus-specific library fragments were then amplified using a subsequent round of PCR.

The enrichment NGS were retrospectively complemented with unbiased NGS and/or additional Sanger sequencing to obtain full-length genomes. The study showed that enrichment NGS not only decreased the amount of data requiring analysis but produced full-length genome coverage in both laboratory and clinical samples.

Using this technology, the researchers “effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.” In addition, they noted that using standard targeted PCR, which is common practice for many surveillance studies, would not have discovered this diversity.

“We should be alert and vigilant with the knowledge that bat CoVs are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to the researchers.

“We have provided a cost-effective methodology for bat CoV surveillance. The high genetic diversity observed in our newly sequenced samples suggests further work is needed to characterize these bat CoVs prior to or in the early stages of spillover to humans,” the authors concluded.

This study was supported by the Chinese government. The authors reported that they had no conflicts.

Viral genome data for new CoVs from this study are available in GenBank under accession numbers MN611517 to MN611525.

mlesney@mdedge.com

SOURCE: Li B et al. mSphere 2020 Jan 29;5:e00807-19.

Enrichment next-generation sequencing (NGS) provides a more cost-efficient and sensitive method for detecting and sequencing novel coronaviruses from wild bat populations, according to a study reported in mSphere, an open-access journal from the American Society for Microbiology.

Wikimedia Commons/Mickey Samuni-Blank

With the appearance of the new zoonotic Wuhan coronavirus, the importance of monitoring the likelihood of new virus risks in wildlife reservoirs has been heightened. Bats in particular have been found to be the most common reservoir of coronaviruses, including being a probable source or mixing vessel for two previous modern epidemic coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

“We should be alert and vigilant with the knowledge that bat CoVs [coronaviruses] are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to Bei Li, MD, of the Wuhan (China) Institute of Virology, and colleagues.

“We previously provided serological evidence that [HKU8-related] CoV had jumped over from bats to camels and recombined with MERS-CoV, alerting other researchers that the CoV species could be dangerous. ... Genome-level comparison is needed to monitor the risk of alterations in species tropism and pathogenesis,” according to study authors. They performed a study to develop a more effective and cost efficient method for detecting and sequencing novel coronaviruses in the bat population.

The taxonomy of coronaviruses is particularly complex and may be too narrowly defined, given the high level of genetic plasticity found. There are four genera (Alpha-, Beta-, Gamma-, and Deltacoronavirus) consisting of 38 unique species in the CoV subfamily Orthocoronavirinae, and the number is increasing. Viral taxomists rely on the open reading frame 1b (ORF1b) gene for classification, but viruses in the same species may show great diversity in regions outside ORF1b, confounding the species designation. In particular, bat CoVs classed as the same species can differ significantly in terms of receptor usage or virus-host interaction, as observed in bat SARS-related CoVs, according to the researchers.

The researchers obtained RNA from previous bat CoV surveillance projects, which used bat rectal swabs. Libraries for NGS were constructed from total RNA and processed to generate RNA fragments larger than 300 nucleotides. Following first- and second-strand cDNA synthesis, double-stranded cDNA was purified and the library was amplified by polymerase chain reaction (PCR) technology.

Targeted CoV genome enrichment was achieved using 4,303 customized biotinylated 120-mer baits. These baits were designed from 90 representative CoV genomes, and in silico analysis determined that these baits should target the known CoV species tested. These baits were added and hybridized to the libraries. To capture virus-specific library fragments, streptavidin magnetic beads (which bind to biotin) were added to the hybridization reaction mixture. The beads were then washed to remove unbound DNA. The postcapture virus-specific library fragments were then amplified using a subsequent round of PCR.

The enrichment NGS were retrospectively complemented with unbiased NGS and/or additional Sanger sequencing to obtain full-length genomes. The study showed that enrichment NGS not only decreased the amount of data requiring analysis but produced full-length genome coverage in both laboratory and clinical samples.

Using this technology, the researchers “effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.” In addition, they noted that using standard targeted PCR, which is common practice for many surveillance studies, would not have discovered this diversity.

“We should be alert and vigilant with the knowledge that bat CoVs are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to the researchers.

“We have provided a cost-effective methodology for bat CoV surveillance. The high genetic diversity observed in our newly sequenced samples suggests further work is needed to characterize these bat CoVs prior to or in the early stages of spillover to humans,” the authors concluded.

This study was supported by the Chinese government. The authors reported that they had no conflicts.

Viral genome data for new CoVs from this study are available in GenBank under accession numbers MN611517 to MN611525.

mlesney@mdedge.com

SOURCE: Li B et al. mSphere 2020 Jan 29;5:e00807-19.

The Food and Drug Administration has approved the first drug to combat peanut allergy in children, (Palforzia, Aimmune Therapeutics), although those who take it must continue to avoid peanuts in their diets.

The peanut (Arachis hypogaea) allergen powder is also the first drug ever approved to treat a food allergy. It is not a cure, but it mitigates allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts, the FDA said in a news release.

Treatment with the oral powder, which is mixed into semisolid food – such as applesauce or yogurt – can be started in children aged 4 through 17 years who have a confirmed peanut allergy and then continued as a maintenance medication. Some 1 million American children have peanut allergy, and only a fifth will outgrow the allergy, the agency said.

“Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement.

An FDA advisory panel backed the medication in September 2019, but some committee members expressed concern about the large number of children in clinical trials who required epinephrine after receiving a dose of Palforzia.

The initial dose phase is given on a single day, while updosing consists of 11 increasing doses over several months. If the patient tolerates the first administration of an increased dose level, they may continue that dose daily at home. Daily maintenance begins after the completion of all updosing levels.

The drug will carry a boxed warning on the risk of anaphylaxis with the drug, and the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS).

Palforzia will be available only through specially certified health care providers, health care settings, and pharmacies to patients enrolled in the REMS program, the agency said. Also, the initial dose escalation and first dose of each updosing level can be given only in a certified setting.

The agency said that patients or parents or caregivers must be counseled on the need for constant availability of injectable epinephrine, the need for continued dietary peanut avoidance, and on how to recognize the signs and symptoms of anaphylaxis.

‘Eagerly’ awaited

Palforzia’s effectiveness was based on a randomized, double-blind, placebo-controlled study involving about 500 peanut-allergic individuals that found that 67.2% of allergic patients tolerated an oral challenge with a single 600-mg dose of peanut protein with no more than mild allergic symptoms after 6 months of maintenance treatment, compared with 4% of placebo recipients, the FDA said.

In two double-blind, placebo-controlled studies looking at safety, the most commonly reported side effects among about 700 individuals involved in the research were abdominal pain, vomiting, nausea, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis.

Palforzia should not be given to those with uncontrolled asthma and can’t be used for emergency treatment of allergic reactions, including anaphylaxis.

“The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, MD, chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences, in a company statement from Aimmune. “With today’s approval of Palforzia, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the first drug to combat peanut allergy in children, (Palforzia, Aimmune Therapeutics), although those who take it must continue to avoid peanuts in their diets.

The peanut (Arachis hypogaea) allergen powder is also the first drug ever approved to treat a food allergy. It is not a cure, but it mitigates allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts, the FDA said in a news release.

Treatment with the oral powder, which is mixed into semisolid food – such as applesauce or yogurt – can be started in children aged 4 through 17 years who have a confirmed peanut allergy and then continued as a maintenance medication. Some 1 million American children have peanut allergy, and only a fifth will outgrow the allergy, the agency said.

“Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement.

An FDA advisory panel backed the medication in September 2019, but some committee members expressed concern about the large number of children in clinical trials who required epinephrine after receiving a dose of Palforzia.

The initial dose phase is given on a single day, while updosing consists of 11 increasing doses over several months. If the patient tolerates the first administration of an increased dose level, they may continue that dose daily at home. Daily maintenance begins after the completion of all updosing levels.

The drug will carry a boxed warning on the risk of anaphylaxis with the drug, and the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS).

Palforzia will be available only through specially certified health care providers, health care settings, and pharmacies to patients enrolled in the REMS program, the agency said. Also, the initial dose escalation and first dose of each updosing level can be given only in a certified setting.

The agency said that patients or parents or caregivers must be counseled on the need for constant availability of injectable epinephrine, the need for continued dietary peanut avoidance, and on how to recognize the signs and symptoms of anaphylaxis.

‘Eagerly’ awaited

Palforzia’s effectiveness was based on a randomized, double-blind, placebo-controlled study involving about 500 peanut-allergic individuals that found that 67.2% of allergic patients tolerated an oral challenge with a single 600-mg dose of peanut protein with no more than mild allergic symptoms after 6 months of maintenance treatment, compared with 4% of placebo recipients, the FDA said.

In two double-blind, placebo-controlled studies looking at safety, the most commonly reported side effects among about 700 individuals involved in the research were abdominal pain, vomiting, nausea, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis.

Palforzia should not be given to those with uncontrolled asthma and can’t be used for emergency treatment of allergic reactions, including anaphylaxis.

“The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, MD, chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences, in a company statement from Aimmune. “With today’s approval of Palforzia, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the first drug to combat peanut allergy in children, (Palforzia, Aimmune Therapeutics), although those who take it must continue to avoid peanuts in their diets.

The peanut (Arachis hypogaea) allergen powder is also the first drug ever approved to treat a food allergy. It is not a cure, but it mitigates allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts, the FDA said in a news release.

Treatment with the oral powder, which is mixed into semisolid food – such as applesauce or yogurt – can be started in children aged 4 through 17 years who have a confirmed peanut allergy and then continued as a maintenance medication. Some 1 million American children have peanut allergy, and only a fifth will outgrow the allergy, the agency said.

“Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement.

An FDA advisory panel backed the medication in September 2019, but some committee members expressed concern about the large number of children in clinical trials who required epinephrine after receiving a dose of Palforzia.

The initial dose phase is given on a single day, while updosing consists of 11 increasing doses over several months. If the patient tolerates the first administration of an increased dose level, they may continue that dose daily at home. Daily maintenance begins after the completion of all updosing levels.

The drug will carry a boxed warning on the risk of anaphylaxis with the drug, and the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS).

Palforzia will be available only through specially certified health care providers, health care settings, and pharmacies to patients enrolled in the REMS program, the agency said. Also, the initial dose escalation and first dose of each updosing level can be given only in a certified setting.

The agency said that patients or parents or caregivers must be counseled on the need for constant availability of injectable epinephrine, the need for continued dietary peanut avoidance, and on how to recognize the signs and symptoms of anaphylaxis.

‘Eagerly’ awaited

Palforzia’s effectiveness was based on a randomized, double-blind, placebo-controlled study involving about 500 peanut-allergic individuals that found that 67.2% of allergic patients tolerated an oral challenge with a single 600-mg dose of peanut protein with no more than mild allergic symptoms after 6 months of maintenance treatment, compared with 4% of placebo recipients, the FDA said.

In two double-blind, placebo-controlled studies looking at safety, the most commonly reported side effects among about 700 individuals involved in the research were abdominal pain, vomiting, nausea, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis.

Palforzia should not be given to those with uncontrolled asthma and can’t be used for emergency treatment of allergic reactions, including anaphylaxis.

“The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, MD, chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences, in a company statement from Aimmune. “With today’s approval of Palforzia, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”

This article first appeared on Medscape.com.