A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

Oral semaglutide monotherapy was superior to placebo for improving glycated hemoglobin (HbA_1c) levels at all doses tested in adults with type 2 diabetes who had been previously insufficiently managed with diet and exercise, according to findings from a global, randomized trial.

The drug also showed dose-dependent weight loss, with a statistically significant effect on body weight, compared with placebo, at higher doses.

To date, the glucagon-like peptide–1 receptor agonist has been available as weekly subcutaneous shots for patients with type 2 diabetes, and in that form they have been shown to be effective in reducing HbA_1c, inducing weight loss, and lowering the risk of cardiovascular events in patients with cardiovascular disease or those who are at high risk for it, wrote Vanita R. Aroda, MD, of Brigham and Women’s Hospital, Boston, and colleagues. The report is in Diabetes Care.

The novel oral semaglutide tablet is designed to enhance medication absorption, and the pharmacokinetics and dosage were established in phase 2 studies, they noted.

In the phase 3 Peptide Innovation for Early Diabetes Treatment 1 (PIONEER 1) study, Dr. Aroda and colleagues randomized 703 adults with type 2 diabetes to receive either 3 mg, 7 mg, or 14 mg of oral semaglutide daily, or placebo. The average age of the patients was 55 years, about half were women, and the average baseline HbA_1c was 8.0% (64 mmol/mol). The primary endpoint was change in HbA_1c level from baseline to week 26, and the secondary endpoint was change in body weight over the same period.

After 26 weeks of once-daily treatment, patients in semaglutide group showed significant reductions in HbA_1c from baseline with all three doses: –0.6% (3 mg), –0.9% (7 mg), and –1.1% (14 mg), with P less than .001 for all, based on an intention-to-treat analysis. Similar results occurred using an on-treatment analysis, with differences of –0.7%, –1.2%, and –1.4%, respectively, for the three doses.

In addition, patients in all dose groups achieved the secondary endpoint of reduction in body weight, compared with placebo, from baseline to 26 weeks based on both types of analyses. “Significantly more patients achieved body weight loss of at least 5% with oral semaglutide at 7 mg and 14 mg, compared with placebo,” Dr. Aroda and colleagues wrote (intention-to-treat: –0.1 for 3 mg daily [P = .87], –0.9 for 7 mg [P = .09], –2.3 for 14 mg [P less than .001]; and on-treatment: –0.2 for 3 mg [P = .71], –1.0 for 7 mg [P = .01], –2.6 for 14 mg [P less than .001]).

The overall incidence of adverse events and serious adverse events was similar in the treatment and placebo groups, with the most frequent being nausea and diarrhea. No deaths occurred among patients on the medication.

The findings were limited by several factors, including a patient population that had a relatively short duration of diabetes (mean, 3.5 years) and that the oral semaglutide was used as first-line monotherapy, without first using metformin, the researchers noted. However, oral semaglutide “achieved clinically meaningful and superior glucose lowering,” compared with placebo, at all three doses, they wrote.

“Ongoing additional studies in the PIONEER program will further define the effect when used in combination with other glucose-lowering therapies and in other populations of interest, such as those with high cardiovascular risk or renal impairment,” they emphasized

Novo Nordisk funded the study. The lead author disclosed relationships with Novo Nordisk, and several coauthors disclosed relationships with or employment by the company.

SOURCE: Aroda VR et al. Diabetes Care. 2019 Jul. doi: 10.2337/dc19-0749.

Oral semaglutide monotherapy was superior to placebo for improving glycated hemoglobin (HbA_1c) levels at all doses tested in adults with type 2 diabetes who had been previously insufficiently managed with diet and exercise, according to findings from a global, randomized trial.

The drug also showed dose-dependent weight loss, with a statistically significant effect on body weight, compared with placebo, at higher doses.

To date, the glucagon-like peptide–1 receptor agonist has been available as weekly subcutaneous shots for patients with type 2 diabetes, and in that form they have been shown to be effective in reducing HbA_1c, inducing weight loss, and lowering the risk of cardiovascular events in patients with cardiovascular disease or those who are at high risk for it, wrote Vanita R. Aroda, MD, of Brigham and Women’s Hospital, Boston, and colleagues. The report is in Diabetes Care.

The novel oral semaglutide tablet is designed to enhance medication absorption, and the pharmacokinetics and dosage were established in phase 2 studies, they noted.

In the phase 3 Peptide Innovation for Early Diabetes Treatment 1 (PIONEER 1) study, Dr. Aroda and colleagues randomized 703 adults with type 2 diabetes to receive either 3 mg, 7 mg, or 14 mg of oral semaglutide daily, or placebo. The average age of the patients was 55 years, about half were women, and the average baseline HbA_1c was 8.0% (64 mmol/mol). The primary endpoint was change in HbA_1c level from baseline to week 26, and the secondary endpoint was change in body weight over the same period.

After 26 weeks of once-daily treatment, patients in semaglutide group showed significant reductions in HbA_1c from baseline with all three doses: –0.6% (3 mg), –0.9% (7 mg), and –1.1% (14 mg), with P less than .001 for all, based on an intention-to-treat analysis. Similar results occurred using an on-treatment analysis, with differences of –0.7%, –1.2%, and –1.4%, respectively, for the three doses.

In addition, patients in all dose groups achieved the secondary endpoint of reduction in body weight, compared with placebo, from baseline to 26 weeks based on both types of analyses. “Significantly more patients achieved body weight loss of at least 5% with oral semaglutide at 7 mg and 14 mg, compared with placebo,” Dr. Aroda and colleagues wrote (intention-to-treat: –0.1 for 3 mg daily [P = .87], –0.9 for 7 mg [P = .09], –2.3 for 14 mg [P less than .001]; and on-treatment: –0.2 for 3 mg [P = .71], –1.0 for 7 mg [P = .01], –2.6 for 14 mg [P less than .001]).

The overall incidence of adverse events and serious adverse events was similar in the treatment and placebo groups, with the most frequent being nausea and diarrhea. No deaths occurred among patients on the medication.

The findings were limited by several factors, including a patient population that had a relatively short duration of diabetes (mean, 3.5 years) and that the oral semaglutide was used as first-line monotherapy, without first using metformin, the researchers noted. However, oral semaglutide “achieved clinically meaningful and superior glucose lowering,” compared with placebo, at all three doses, they wrote.

“Ongoing additional studies in the PIONEER program will further define the effect when used in combination with other glucose-lowering therapies and in other populations of interest, such as those with high cardiovascular risk or renal impairment,” they emphasized

Novo Nordisk funded the study. The lead author disclosed relationships with Novo Nordisk, and several coauthors disclosed relationships with or employment by the company.

SOURCE: Aroda VR et al. Diabetes Care. 2019 Jul. doi: 10.2337/dc19-0749.

Oral semaglutide monotherapy was superior to placebo for improving glycated hemoglobin (HbA_1c) levels at all doses tested in adults with type 2 diabetes who had been previously insufficiently managed with diet and exercise, according to findings from a global, randomized trial.

The drug also showed dose-dependent weight loss, with a statistically significant effect on body weight, compared with placebo, at higher doses.

To date, the glucagon-like peptide–1 receptor agonist has been available as weekly subcutaneous shots for patients with type 2 diabetes, and in that form they have been shown to be effective in reducing HbA_1c, inducing weight loss, and lowering the risk of cardiovascular events in patients with cardiovascular disease or those who are at high risk for it, wrote Vanita R. Aroda, MD, of Brigham and Women’s Hospital, Boston, and colleagues. The report is in Diabetes Care.

The novel oral semaglutide tablet is designed to enhance medication absorption, and the pharmacokinetics and dosage were established in phase 2 studies, they noted.

In the phase 3 Peptide Innovation for Early Diabetes Treatment 1 (PIONEER 1) study, Dr. Aroda and colleagues randomized 703 adults with type 2 diabetes to receive either 3 mg, 7 mg, or 14 mg of oral semaglutide daily, or placebo. The average age of the patients was 55 years, about half were women, and the average baseline HbA_1c was 8.0% (64 mmol/mol). The primary endpoint was change in HbA_1c level from baseline to week 26, and the secondary endpoint was change in body weight over the same period.

After 26 weeks of once-daily treatment, patients in semaglutide group showed significant reductions in HbA_1c from baseline with all three doses: –0.6% (3 mg), –0.9% (7 mg), and –1.1% (14 mg), with P less than .001 for all, based on an intention-to-treat analysis. Similar results occurred using an on-treatment analysis, with differences of –0.7%, –1.2%, and –1.4%, respectively, for the three doses.

In addition, patients in all dose groups achieved the secondary endpoint of reduction in body weight, compared with placebo, from baseline to 26 weeks based on both types of analyses. “Significantly more patients achieved body weight loss of at least 5% with oral semaglutide at 7 mg and 14 mg, compared with placebo,” Dr. Aroda and colleagues wrote (intention-to-treat: –0.1 for 3 mg daily [P = .87], –0.9 for 7 mg [P = .09], –2.3 for 14 mg [P less than .001]; and on-treatment: –0.2 for 3 mg [P = .71], –1.0 for 7 mg [P = .01], –2.6 for 14 mg [P less than .001]).

The overall incidence of adverse events and serious adverse events was similar in the treatment and placebo groups, with the most frequent being nausea and diarrhea. No deaths occurred among patients on the medication.

The findings were limited by several factors, including a patient population that had a relatively short duration of diabetes (mean, 3.5 years) and that the oral semaglutide was used as first-line monotherapy, without first using metformin, the researchers noted. However, oral semaglutide “achieved clinically meaningful and superior glucose lowering,” compared with placebo, at all three doses, they wrote.

“Ongoing additional studies in the PIONEER program will further define the effect when used in combination with other glucose-lowering therapies and in other populations of interest, such as those with high cardiovascular risk or renal impairment,” they emphasized

Novo Nordisk funded the study. The lead author disclosed relationships with Novo Nordisk, and several coauthors disclosed relationships with or employment by the company.

SOURCE: Aroda VR et al. Diabetes Care. 2019 Jul. doi: 10.2337/dc19-0749.

Jorge E. Cortes, MD, is set to become director of the Georgia Cancer Center in Augusta on Sept. 1. In this new position, Dr. Cortes will further the center’s missions of obtaining National Cancer Institute designation and reducing the burden of cancer in Georgia.

Dr. Cortes was previously deputy chair and professor of medicine in the department of leukemia at MD Anderson Cancer Center in Houston. He received his medical degree in 1986 and began working at MD Anderson in 1991. His clinical interests include acute and chronic leukemias, myelodysplastic syndromes, and myeloproliferative neoplasms.

Fern M. Anari, MD, joined Fox Chase Cancer Center in Philadelphia in August. Dr. Anari is now an assistant professor in the division of genitourinary medical oncology within the department of hematology/oncology.

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.

[email protected]

Jorge E. Cortes, MD, is set to become director of the Georgia Cancer Center in Augusta on Sept. 1. In this new position, Dr. Cortes will further the center’s missions of obtaining National Cancer Institute designation and reducing the burden of cancer in Georgia.

Dr. Cortes was previously deputy chair and professor of medicine in the department of leukemia at MD Anderson Cancer Center in Houston. He received his medical degree in 1986 and began working at MD Anderson in 1991. His clinical interests include acute and chronic leukemias, myelodysplastic syndromes, and myeloproliferative neoplasms.

Fern M. Anari, MD, joined Fox Chase Cancer Center in Philadelphia in August. Dr. Anari is now an assistant professor in the division of genitourinary medical oncology within the department of hematology/oncology.

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.

[email protected]

Jorge E. Cortes, MD, is set to become director of the Georgia Cancer Center in Augusta on Sept. 1. In this new position, Dr. Cortes will further the center’s missions of obtaining National Cancer Institute designation and reducing the burden of cancer in Georgia.

Dr. Cortes was previously deputy chair and professor of medicine in the department of leukemia at MD Anderson Cancer Center in Houston. He received his medical degree in 1986 and began working at MD Anderson in 1991. His clinical interests include acute and chronic leukemias, myelodysplastic syndromes, and myeloproliferative neoplasms.

Fern M. Anari, MD, joined Fox Chase Cancer Center in Philadelphia in August. Dr. Anari is now an assistant professor in the division of genitourinary medical oncology within the department of hematology/oncology.

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.

[email protected]

A new assessment statement from the American Heart Association reviewed the strengths and limitations of current imaging techniques for critical limb ischemia (CLI), the severest form of peripheral arterial disease (PAD).

The main techniques discussed were the ankle-brachial index (ABI), toe-brachial index (TBI), toe systolic pressure, transcutaneous oximetry (TcPO₂) and skin perfusion pressure (SPP). The literature review also identified what the authors saw as opportunities for technology improvement.

“No single vascular test has been identified as the most important predictor of wound healing or major amputation for the threatened limb,” wrote Sanjay Misra, MD, of the Mayo Clinic in Rochester, Minn., and colleagues, on behalf of the American Heart Association Council on Peripheral Vascular Disease, the Council on Clinical Cardiology, and the Council on Cardiovascular and Stroke Nursing.

Of particular concern were limitations seen in the use of ABI, the most widely used assessment method. “Although ABI was first described to diagnose PAD, it has not been shown to be an accurate predictor of wound healing or major adverse limb events. Clearly, the ABI provides important prognostic information, including the risk of death, myocardial infarction, and stroke ... and should be performed in all patients suspected of having PAD,” but in about 30% of patients with angiographically documented CLI, the ABI is normal or noncompressible, the authors wrote.

And, although recent data indicate that toe pressure may be a better predictor of major adverse limb events and tibial disease in patients with CLI, especially among those with isolated below-knee disease, there was no solid evidence that ABI or TBI have the sensitivity or specificity to be used as perfusion tools to assess wound healing or limb salvage, the authors stated.

However, there may be some technological improvements on the horizon for assessing limb perfusion that might provide eventual benefits, according to the reviewers. These include the use of indigo carmine angiography to evaluate microcirculation and angiosomal revascularization, the use of CT perfusion or MRI to quantify perfusion and monitor treatment response, the use of contrast-enhanced ultrasound to assess calf muscle perfusion, and hyperspectral imaging.

Among the other issues of concern raised in the AHA statement were the significant demographic disparities that occur in detection and treatment of CLI. The authors noted differences in how CLI is diagnosed, the coexisting conditions that were present, and the disparities in treatment given based on sex and racial differences. For example, women were more likely to experience emergency hospitalization, have differences in blood flow, and have higher disability and death rates.

As for racial disparities, the reviewers found that black and Hispanic patients with CLI were more likely to have diabetes and chronic kidney disease, and were more likely to develop gangrene, compared with white patients, who were more likely to have ulcers and pain in their legs while at rest.

In terms of treatment, black patients were 78% more likely to receive lower extremity amputation for CLI, compared with their white peers, even after adjustment for socioeconomic status, access to facilities with revascularization services, and other factors, according to the report, which was published online in Circulation.

“CLI is a complex disease process with great morbidity. This statement highlights the importance of incorporating perfusion assessment into the care of CLI patients. Despite the high prevalence of CLI, strategies for perfusion assessment remain limited. New technologies offer potential opportunities to improve the precision and quality of CLI management,” the researchers concluded.

Dr. Misra and the majority of the authors reported having no relevant disclosures. Several authors reported receiving funding from the pharmaceutical and medical device industries.

[email protected]

SOURCE: Chandra S. et al. Circulation. 2019;140:00-00. doi: 10.1161/CIR.0000000000000708.

A new assessment statement from the American Heart Association reviewed the strengths and limitations of current imaging techniques for critical limb ischemia (CLI), the severest form of peripheral arterial disease (PAD).

The main techniques discussed were the ankle-brachial index (ABI), toe-brachial index (TBI), toe systolic pressure, transcutaneous oximetry (TcPO₂) and skin perfusion pressure (SPP). The literature review also identified what the authors saw as opportunities for technology improvement.

“No single vascular test has been identified as the most important predictor of wound healing or major amputation for the threatened limb,” wrote Sanjay Misra, MD, of the Mayo Clinic in Rochester, Minn., and colleagues, on behalf of the American Heart Association Council on Peripheral Vascular Disease, the Council on Clinical Cardiology, and the Council on Cardiovascular and Stroke Nursing.

Of particular concern were limitations seen in the use of ABI, the most widely used assessment method. “Although ABI was first described to diagnose PAD, it has not been shown to be an accurate predictor of wound healing or major adverse limb events. Clearly, the ABI provides important prognostic information, including the risk of death, myocardial infarction, and stroke ... and should be performed in all patients suspected of having PAD,” but in about 30% of patients with angiographically documented CLI, the ABI is normal or noncompressible, the authors wrote.

And, although recent data indicate that toe pressure may be a better predictor of major adverse limb events and tibial disease in patients with CLI, especially among those with isolated below-knee disease, there was no solid evidence that ABI or TBI have the sensitivity or specificity to be used as perfusion tools to assess wound healing or limb salvage, the authors stated.

However, there may be some technological improvements on the horizon for assessing limb perfusion that might provide eventual benefits, according to the reviewers. These include the use of indigo carmine angiography to evaluate microcirculation and angiosomal revascularization, the use of CT perfusion or MRI to quantify perfusion and monitor treatment response, the use of contrast-enhanced ultrasound to assess calf muscle perfusion, and hyperspectral imaging.

Among the other issues of concern raised in the AHA statement were the significant demographic disparities that occur in detection and treatment of CLI. The authors noted differences in how CLI is diagnosed, the coexisting conditions that were present, and the disparities in treatment given based on sex and racial differences. For example, women were more likely to experience emergency hospitalization, have differences in blood flow, and have higher disability and death rates.

As for racial disparities, the reviewers found that black and Hispanic patients with CLI were more likely to have diabetes and chronic kidney disease, and were more likely to develop gangrene, compared with white patients, who were more likely to have ulcers and pain in their legs while at rest.

In terms of treatment, black patients were 78% more likely to receive lower extremity amputation for CLI, compared with their white peers, even after adjustment for socioeconomic status, access to facilities with revascularization services, and other factors, according to the report, which was published online in Circulation.

“CLI is a complex disease process with great morbidity. This statement highlights the importance of incorporating perfusion assessment into the care of CLI patients. Despite the high prevalence of CLI, strategies for perfusion assessment remain limited. New technologies offer potential opportunities to improve the precision and quality of CLI management,” the researchers concluded.

Dr. Misra and the majority of the authors reported having no relevant disclosures. Several authors reported receiving funding from the pharmaceutical and medical device industries.

[email protected]

SOURCE: Chandra S. et al. Circulation. 2019;140:00-00. doi: 10.1161/CIR.0000000000000708.

A new assessment statement from the American Heart Association reviewed the strengths and limitations of current imaging techniques for critical limb ischemia (CLI), the severest form of peripheral arterial disease (PAD).

The main techniques discussed were the ankle-brachial index (ABI), toe-brachial index (TBI), toe systolic pressure, transcutaneous oximetry (TcPO₂) and skin perfusion pressure (SPP). The literature review also identified what the authors saw as opportunities for technology improvement.

“No single vascular test has been identified as the most important predictor of wound healing or major amputation for the threatened limb,” wrote Sanjay Misra, MD, of the Mayo Clinic in Rochester, Minn., and colleagues, on behalf of the American Heart Association Council on Peripheral Vascular Disease, the Council on Clinical Cardiology, and the Council on Cardiovascular and Stroke Nursing.

Of particular concern were limitations seen in the use of ABI, the most widely used assessment method. “Although ABI was first described to diagnose PAD, it has not been shown to be an accurate predictor of wound healing or major adverse limb events. Clearly, the ABI provides important prognostic information, including the risk of death, myocardial infarction, and stroke ... and should be performed in all patients suspected of having PAD,” but in about 30% of patients with angiographically documented CLI, the ABI is normal or noncompressible, the authors wrote.

And, although recent data indicate that toe pressure may be a better predictor of major adverse limb events and tibial disease in patients with CLI, especially among those with isolated below-knee disease, there was no solid evidence that ABI or TBI have the sensitivity or specificity to be used as perfusion tools to assess wound healing or limb salvage, the authors stated.

However, there may be some technological improvements on the horizon for assessing limb perfusion that might provide eventual benefits, according to the reviewers. These include the use of indigo carmine angiography to evaluate microcirculation and angiosomal revascularization, the use of CT perfusion or MRI to quantify perfusion and monitor treatment response, the use of contrast-enhanced ultrasound to assess calf muscle perfusion, and hyperspectral imaging.

Among the other issues of concern raised in the AHA statement were the significant demographic disparities that occur in detection and treatment of CLI. The authors noted differences in how CLI is diagnosed, the coexisting conditions that were present, and the disparities in treatment given based on sex and racial differences. For example, women were more likely to experience emergency hospitalization, have differences in blood flow, and have higher disability and death rates.

As for racial disparities, the reviewers found that black and Hispanic patients with CLI were more likely to have diabetes and chronic kidney disease, and were more likely to develop gangrene, compared with white patients, who were more likely to have ulcers and pain in their legs while at rest.

In terms of treatment, black patients were 78% more likely to receive lower extremity amputation for CLI, compared with their white peers, even after adjustment for socioeconomic status, access to facilities with revascularization services, and other factors, according to the report, which was published online in Circulation.

“CLI is a complex disease process with great morbidity. This statement highlights the importance of incorporating perfusion assessment into the care of CLI patients. Despite the high prevalence of CLI, strategies for perfusion assessment remain limited. New technologies offer potential opportunities to improve the precision and quality of CLI management,” the researchers concluded.

Dr. Misra and the majority of the authors reported having no relevant disclosures. Several authors reported receiving funding from the pharmaceutical and medical device industries.

[email protected]

SOURCE: Chandra S. et al. Circulation. 2019;140:00-00. doi: 10.1161/CIR.0000000000000708.

Click here to access August 2019 Advances in Hematology and Oncology

Table of Contents

• Partners in Oncology Care: Coordinated Follicular Lymphoma Management
• Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer
• Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival
• Review of Radiologic Considerations in an Immunocompetent Patient With Primary Central Nervous System Lymphoma
• Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms
• Timely Diagnosis of Lung Cancer in a Dedicated VA Referral Unit With Endobronchial Ultrasound
• Research News: Darolutamide Approved for Nonmetastatic CRPC
• Roundtable: Genomic Medicine and Genetic Counseling in the VA and DoD

Click here to access August 2019 Advances in Hematology and Oncology

Table of Contents

• Partners in Oncology Care: Coordinated Follicular Lymphoma Management
• Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer
• Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival
• Review of Radiologic Considerations in an Immunocompetent Patient With Primary Central Nervous System Lymphoma
• Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms
• Timely Diagnosis of Lung Cancer in a Dedicated VA Referral Unit With Endobronchial Ultrasound
• Research News: Darolutamide Approved for Nonmetastatic CRPC
• Roundtable: Genomic Medicine and Genetic Counseling in the VA and DoD

Click here to access August 2019 Advances in Hematology and Oncology

Table of Contents

• Partners in Oncology Care: Coordinated Follicular Lymphoma Management
• Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer
• Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival
• Review of Radiologic Considerations in an Immunocompetent Patient With Primary Central Nervous System Lymphoma
• Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms
• Timely Diagnosis of Lung Cancer in a Dedicated VA Referral Unit With Endobronchial Ultrasound
• Research News: Darolutamide Approved for Nonmetastatic CRPC
• Roundtable: Genomic Medicine and Genetic Counseling in the VA and DoD

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

The vascular specialty has had many coding changes over the past five to six years. It is sometimes difficult to keep up with the changes from year to year, but attending the SVS Coding & Reimbursement workshop, to be held on Sept. 20-21 in Rosemont, Ill., is sure to help. Coding is critical in every practice model – whether it be private, academic or employed. If it is not done accurately, money will be lost. This intensive course will give attendees the knowledge they need to make a positive impact on their coding procedures. All those who wish to improve and expand their knowledge of accurate coding and reimbursement for vascular surgery should attend. Learn more and register here.

The vascular specialty has had many coding changes over the past five to six years. It is sometimes difficult to keep up with the changes from year to year, but attending the SVS Coding & Reimbursement workshop, to be held on Sept. 20-21 in Rosemont, Ill., is sure to help. Coding is critical in every practice model – whether it be private, academic or employed. If it is not done accurately, money will be lost. This intensive course will give attendees the knowledge they need to make a positive impact on their coding procedures. All those who wish to improve and expand their knowledge of accurate coding and reimbursement for vascular surgery should attend. Learn more and register here.

The vascular specialty has had many coding changes over the past five to six years. It is sometimes difficult to keep up with the changes from year to year, but attending the SVS Coding & Reimbursement workshop, to be held on Sept. 20-21 in Rosemont, Ill., is sure to help. Coding is critical in every practice model – whether it be private, academic or employed. If it is not done accurately, money will be lost. This intensive course will give attendees the knowledge they need to make a positive impact on their coding procedures. All those who wish to improve and expand their knowledge of accurate coding and reimbursement for vascular surgery should attend. Learn more and register here.

Psoriasis is associated with systemic inflammation, which heightens the risk of blood vessel disease and diabetes. Therefore, the finding, while notable, may not have been entirely unexpected. Biologic therapy (BT) for psoriasis was already found to be favorably associated with luminal coronary plaque, the researchers say, but it was not clear whether those associations were attributable to direct anti-inflammatory effects on the coronary arteries. They wanted to find out whether the perivascular fat attenuation index (FAI) would offer clues. FAI is a new method of analyzing CT scans by assessing whether the fat tissue surrounding arteries becomes attenuated, or less fatty.

The researchers investigated their premise in 134 participants from an ongoing NIH study, the Psoriasis Atherosclerosis Cardiometabolic Initiative cohort. Of the participants, 82 had been receiving anti-tumor necrosis factor α, anti-interleukin (IL) 12/23, or anti-IL-17 for 1 year. The remaining 52 had not received any BT, and given topical or light therapy. The patients underwent CT scans at the start of the study and 1 year later. All of the patients had low cardiovascular risk. At baseline, 27 in the treated group and 19 in the untreated group had a focal coronary atherosclerotic plaque.

The study found that an abnormal perivascular FAI was linked to a 6- to 9-fold increased risk of major adverse cardiovascular events, study coauthor Charalambos Antoniades, MD, says. Patients on BT had a significant decrease in FAI at 1 year, as well as improved psoriasis symptoms. Even patients with preexisting coronary artery plaque had a reduction in coronary inflammation after BT. No change was seen in the untreated patients. The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

The researchers say their findings have implications for other chronic inflammatory diseases, such as lupus and rheumatoid arthritis, which are known to raise the risk for heart attacks and stroke.

Psoriasis is associated with systemic inflammation, which heightens the risk of blood vessel disease and diabetes. Therefore, the finding, while notable, may not have been entirely unexpected. Biologic therapy (BT) for psoriasis was already found to be favorably associated with luminal coronary plaque, the researchers say, but it was not clear whether those associations were attributable to direct anti-inflammatory effects on the coronary arteries. They wanted to find out whether the perivascular fat attenuation index (FAI) would offer clues. FAI is a new method of analyzing CT scans by assessing whether the fat tissue surrounding arteries becomes attenuated, or less fatty.

The researchers investigated their premise in 134 participants from an ongoing NIH study, the Psoriasis Atherosclerosis Cardiometabolic Initiative cohort. Of the participants, 82 had been receiving anti-tumor necrosis factor α, anti-interleukin (IL) 12/23, or anti-IL-17 for 1 year. The remaining 52 had not received any BT, and given topical or light therapy. The patients underwent CT scans at the start of the study and 1 year later. All of the patients had low cardiovascular risk. At baseline, 27 in the treated group and 19 in the untreated group had a focal coronary atherosclerotic plaque.

The study found that an abnormal perivascular FAI was linked to a 6- to 9-fold increased risk of major adverse cardiovascular events, study coauthor Charalambos Antoniades, MD, says. Patients on BT had a significant decrease in FAI at 1 year, as well as improved psoriasis symptoms. Even patients with preexisting coronary artery plaque had a reduction in coronary inflammation after BT. No change was seen in the untreated patients. The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

The researchers say their findings have implications for other chronic inflammatory diseases, such as lupus and rheumatoid arthritis, which are known to raise the risk for heart attacks and stroke.

Psoriasis is associated with systemic inflammation, which heightens the risk of blood vessel disease and diabetes. Therefore, the finding, while notable, may not have been entirely unexpected. Biologic therapy (BT) for psoriasis was already found to be favorably associated with luminal coronary plaque, the researchers say, but it was not clear whether those associations were attributable to direct anti-inflammatory effects on the coronary arteries. They wanted to find out whether the perivascular fat attenuation index (FAI) would offer clues. FAI is a new method of analyzing CT scans by assessing whether the fat tissue surrounding arteries becomes attenuated, or less fatty.

The researchers investigated their premise in 134 participants from an ongoing NIH study, the Psoriasis Atherosclerosis Cardiometabolic Initiative cohort. Of the participants, 82 had been receiving anti-tumor necrosis factor α, anti-interleukin (IL) 12/23, or anti-IL-17 for 1 year. The remaining 52 had not received any BT, and given topical or light therapy. The patients underwent CT scans at the start of the study and 1 year later. All of the patients had low cardiovascular risk. At baseline, 27 in the treated group and 19 in the untreated group had a focal coronary atherosclerotic plaque.

The study found that an abnormal perivascular FAI was linked to a 6- to 9-fold increased risk of major adverse cardiovascular events, study coauthor Charalambos Antoniades, MD, says. Patients on BT had a significant decrease in FAI at 1 year, as well as improved psoriasis symptoms. Even patients with preexisting coronary artery plaque had a reduction in coronary inflammation after BT. No change was seen in the untreated patients. The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

The researchers say their findings have implications for other chronic inflammatory diseases, such as lupus and rheumatoid arthritis, which are known to raise the risk for heart attacks and stroke.

PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.

In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.

Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.

The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.

In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.

Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.

Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.

The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.

PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.

[email protected]

SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12

PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.

In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.

Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.

The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.

In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.

Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.

Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.

The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.

PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.

[email protected]

SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12

PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.

In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.

Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.

The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.

In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.

Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.

Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.

The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.

PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.

[email protected]

SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12