NEW ORLEANS – Spironolactone was almost as likely as chlorthalidone to cause hyponatremia in a review of hypertension patients at the University of Alabama at Birmingham, and prior hyponatremia on chlorthalidone increased the risk.

The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.

Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.

The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.

“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.

Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.

Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.

The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m². Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.

Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.

The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.

Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m², and baseline sodium level 135.8 mEq/L.

All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m²), and were more likely to be white, but the differences were not statistically significant.

There was no external funding, and the investigators didn’t have any industry disclosures.

[email protected]

SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.

NEW ORLEANS – Spironolactone was almost as likely as chlorthalidone to cause hyponatremia in a review of hypertension patients at the University of Alabama at Birmingham, and prior hyponatremia on chlorthalidone increased the risk.

The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.

Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.

The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.

“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.

Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.

Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.

The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m². Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.

Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.

The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.

Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m², and baseline sodium level 135.8 mEq/L.

All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m²), and were more likely to be white, but the differences were not statistically significant.

There was no external funding, and the investigators didn’t have any industry disclosures.

[email protected]

SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.

NEW ORLEANS – Spironolactone was almost as likely as chlorthalidone to cause hyponatremia in a review of hypertension patients at the University of Alabama at Birmingham, and prior hyponatremia on chlorthalidone increased the risk.

The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.

Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.

The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.

“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.

Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.

Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.

The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m². Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.

Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.

The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.

Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m², and baseline sodium level 135.8 mEq/L.

All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m²), and were more likely to be white, but the differences were not statistically significant.

There was no external funding, and the investigators didn’t have any industry disclosures.

[email protected]

SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.

BOSTON – The all-oral combination of selinexor, lenalidomide, and dexamethasone has demonstrated efficacy in patients with relapsed/refractory multiple myeloma, particularly those who are lenalidomide naive.

Jennifer Smith/MDedge News

In the phase 1/2 STOMP trial (NCT02343042), selinexor plus lenalidomide and dexamethasone produced an overall response rate (ORR) of 60% in all evaluable patients and an ORR of 92% in lenalidomide-naive patients.

Darrell White, MD, of Dalhousie University in Halifax, N.S., presented these results at the International Myeloma Workshop held by the International Myeloma Society.

Dr. White discussed results in myeloma patients who had received at least one prior line of therapy. This arm of the STOMP trial has enrolled 24 patients. Their median age at baseline was 67 years (range, 49-84 years), and their median time from diagnosis was 4.5 years (range, less than 1-22 years).

The patients had received a median of 1 (range, 1-8) prior therapies. Half of patients had received a transplant. All patients had received a proteasome inhibitor (65% refractory), and 38% had received prior lenalidomide (21% refractory).

Dosing

Patients received selinexor at 60 mg once or twice weekly or at 80 mg once weekly on a 28-day cycle. They received dexamethasone at 20 mg twice weekly or 40 mg once weekly and lenalidomide at 25 mg once daily every 21 days.

The recommended phase 2 dosing schedule was selinexor at 60 mg once weekly plus lenalidomide at 25 mg daily and dexamethasone at 40 mg once weekly. Half of patients (n = 12) received this dosing schedule.

There were no dose-limiting toxicities (DLTs) at the recommended phase 2 dose. When selinexor was given at 60 mg twice weekly, DLTs included grade 3 fatigue, grade 3 anorexia and weight loss, and grade 4 thrombocytopenia (n = 2). When selinexor was given at 80 mg once weekly, the DLTs were grade 4 thrombocytopenia (n = 2).

Safety

“The side-effect profile was as expected, with mainly grade 3/4 toxicity being hematologic and primarily thrombocytopenia and neutropenia,” Dr. White said. “Frequent gastrointestinal side effects [were] expected. Investigators were able to manage that with appropriate supportive care and antiemetics in particular.”

Among patients who received the recommended phase 2 dose, the grade 4 treatment-related adverse events (AEs) were thrombocytopenia (n = 4) and neutropenia (n = 4). Grade 3 treatment-related AEs were thrombocytopenia (n = 3), neutropenia (n = 4), anemia (n = 1), nausea (n = 1), asthenia (n = 1), fatigue (n = 2), and dehydration (n = 1). Common grade 1/2 treatment-related AEs in patients who received the recommended phase 2 dose were nausea (n = 6), anorexia (n = 5), weight loss (n = 5), vomiting (n = 4), diarrhea (n = 4), and fatigue (n = 4).

Efficacy

In the 20 patients evaluable for response, the ORR was 60% (n = 12). One patient achieved a stringent complete response, three had a very good partial response, and eight had a partial response. The median time to response was 1 month.

The ORR was 92% (11/12) in lenalidomide-naive patients and 13% (1/8) in lenalidomide-exposed patients. The single responder in the lenalidomide-exposed group achieved a partial response.

Among lenalidomide-naive patients who received the recommended phase 2 dose, the median time on treatment was 12 months. The patient who achieved a stringent complete response remained on treatment at last follow-up, as did one partial responder and one patient with a very good partial response.

These results suggest the combination of selinexor, lenalidomide, and dexamethasone “is active, relatively well tolerated, and could warrant further investigation,” Dr. White said.

The STOMP trial is sponsored by Karyopharm Therapeutics. Dr. White disclosed relationships with Karyopharm, Amgen, Celgene, Janssen, Sanofi, and Takeda.

[email protected]

SOURCE: White D et al. IMW 2019, Abstract OAB-083.

BOSTON – The all-oral combination of selinexor, lenalidomide, and dexamethasone has demonstrated efficacy in patients with relapsed/refractory multiple myeloma, particularly those who are lenalidomide naive.

Jennifer Smith/MDedge News

In the phase 1/2 STOMP trial (NCT02343042), selinexor plus lenalidomide and dexamethasone produced an overall response rate (ORR) of 60% in all evaluable patients and an ORR of 92% in lenalidomide-naive patients.

Darrell White, MD, of Dalhousie University in Halifax, N.S., presented these results at the International Myeloma Workshop held by the International Myeloma Society.

Dr. White discussed results in myeloma patients who had received at least one prior line of therapy. This arm of the STOMP trial has enrolled 24 patients. Their median age at baseline was 67 years (range, 49-84 years), and their median time from diagnosis was 4.5 years (range, less than 1-22 years).

The patients had received a median of 1 (range, 1-8) prior therapies. Half of patients had received a transplant. All patients had received a proteasome inhibitor (65% refractory), and 38% had received prior lenalidomide (21% refractory).

Dosing

Patients received selinexor at 60 mg once or twice weekly or at 80 mg once weekly on a 28-day cycle. They received dexamethasone at 20 mg twice weekly or 40 mg once weekly and lenalidomide at 25 mg once daily every 21 days.

The recommended phase 2 dosing schedule was selinexor at 60 mg once weekly plus lenalidomide at 25 mg daily and dexamethasone at 40 mg once weekly. Half of patients (n = 12) received this dosing schedule.

There were no dose-limiting toxicities (DLTs) at the recommended phase 2 dose. When selinexor was given at 60 mg twice weekly, DLTs included grade 3 fatigue, grade 3 anorexia and weight loss, and grade 4 thrombocytopenia (n = 2). When selinexor was given at 80 mg once weekly, the DLTs were grade 4 thrombocytopenia (n = 2).

Safety

“The side-effect profile was as expected, with mainly grade 3/4 toxicity being hematologic and primarily thrombocytopenia and neutropenia,” Dr. White said. “Frequent gastrointestinal side effects [were] expected. Investigators were able to manage that with appropriate supportive care and antiemetics in particular.”

Among patients who received the recommended phase 2 dose, the grade 4 treatment-related adverse events (AEs) were thrombocytopenia (n = 4) and neutropenia (n = 4). Grade 3 treatment-related AEs were thrombocytopenia (n = 3), neutropenia (n = 4), anemia (n = 1), nausea (n = 1), asthenia (n = 1), fatigue (n = 2), and dehydration (n = 1). Common grade 1/2 treatment-related AEs in patients who received the recommended phase 2 dose were nausea (n = 6), anorexia (n = 5), weight loss (n = 5), vomiting (n = 4), diarrhea (n = 4), and fatigue (n = 4).

Efficacy

In the 20 patients evaluable for response, the ORR was 60% (n = 12). One patient achieved a stringent complete response, three had a very good partial response, and eight had a partial response. The median time to response was 1 month.

The ORR was 92% (11/12) in lenalidomide-naive patients and 13% (1/8) in lenalidomide-exposed patients. The single responder in the lenalidomide-exposed group achieved a partial response.

Among lenalidomide-naive patients who received the recommended phase 2 dose, the median time on treatment was 12 months. The patient who achieved a stringent complete response remained on treatment at last follow-up, as did one partial responder and one patient with a very good partial response.

These results suggest the combination of selinexor, lenalidomide, and dexamethasone “is active, relatively well tolerated, and could warrant further investigation,” Dr. White said.

The STOMP trial is sponsored by Karyopharm Therapeutics. Dr. White disclosed relationships with Karyopharm, Amgen, Celgene, Janssen, Sanofi, and Takeda.

[email protected]

SOURCE: White D et al. IMW 2019, Abstract OAB-083.

BOSTON – The all-oral combination of selinexor, lenalidomide, and dexamethasone has demonstrated efficacy in patients with relapsed/refractory multiple myeloma, particularly those who are lenalidomide naive.

Jennifer Smith/MDedge News

In the phase 1/2 STOMP trial (NCT02343042), selinexor plus lenalidomide and dexamethasone produced an overall response rate (ORR) of 60% in all evaluable patients and an ORR of 92% in lenalidomide-naive patients.

Darrell White, MD, of Dalhousie University in Halifax, N.S., presented these results at the International Myeloma Workshop held by the International Myeloma Society.

Dr. White discussed results in myeloma patients who had received at least one prior line of therapy. This arm of the STOMP trial has enrolled 24 patients. Their median age at baseline was 67 years (range, 49-84 years), and their median time from diagnosis was 4.5 years (range, less than 1-22 years).

The patients had received a median of 1 (range, 1-8) prior therapies. Half of patients had received a transplant. All patients had received a proteasome inhibitor (65% refractory), and 38% had received prior lenalidomide (21% refractory).

Dosing

Patients received selinexor at 60 mg once or twice weekly or at 80 mg once weekly on a 28-day cycle. They received dexamethasone at 20 mg twice weekly or 40 mg once weekly and lenalidomide at 25 mg once daily every 21 days.

The recommended phase 2 dosing schedule was selinexor at 60 mg once weekly plus lenalidomide at 25 mg daily and dexamethasone at 40 mg once weekly. Half of patients (n = 12) received this dosing schedule.

There were no dose-limiting toxicities (DLTs) at the recommended phase 2 dose. When selinexor was given at 60 mg twice weekly, DLTs included grade 3 fatigue, grade 3 anorexia and weight loss, and grade 4 thrombocytopenia (n = 2). When selinexor was given at 80 mg once weekly, the DLTs were grade 4 thrombocytopenia (n = 2).

Safety

“The side-effect profile was as expected, with mainly grade 3/4 toxicity being hematologic and primarily thrombocytopenia and neutropenia,” Dr. White said. “Frequent gastrointestinal side effects [were] expected. Investigators were able to manage that with appropriate supportive care and antiemetics in particular.”

Among patients who received the recommended phase 2 dose, the grade 4 treatment-related adverse events (AEs) were thrombocytopenia (n = 4) and neutropenia (n = 4). Grade 3 treatment-related AEs were thrombocytopenia (n = 3), neutropenia (n = 4), anemia (n = 1), nausea (n = 1), asthenia (n = 1), fatigue (n = 2), and dehydration (n = 1). Common grade 1/2 treatment-related AEs in patients who received the recommended phase 2 dose were nausea (n = 6), anorexia (n = 5), weight loss (n = 5), vomiting (n = 4), diarrhea (n = 4), and fatigue (n = 4).

Efficacy

In the 20 patients evaluable for response, the ORR was 60% (n = 12). One patient achieved a stringent complete response, three had a very good partial response, and eight had a partial response. The median time to response was 1 month.

The ORR was 92% (11/12) in lenalidomide-naive patients and 13% (1/8) in lenalidomide-exposed patients. The single responder in the lenalidomide-exposed group achieved a partial response.

Among lenalidomide-naive patients who received the recommended phase 2 dose, the median time on treatment was 12 months. The patient who achieved a stringent complete response remained on treatment at last follow-up, as did one partial responder and one patient with a very good partial response.

These results suggest the combination of selinexor, lenalidomide, and dexamethasone “is active, relatively well tolerated, and could warrant further investigation,” Dr. White said.

The STOMP trial is sponsored by Karyopharm Therapeutics. Dr. White disclosed relationships with Karyopharm, Amgen, Celgene, Janssen, Sanofi, and Takeda.

[email protected]

SOURCE: White D et al. IMW 2019, Abstract OAB-083.

CHICAGO – Numerous studies have shown conflicting results for endovascular repair in ruptured abdominal aortic aneurysms (AAA), but an analysis of 4,000-plus cases from a national registry has found a 41% reduction in mortality with endovascular repair vs. open repair, according to a presentation at the annual meeting of the Midwestern Vascular Surgery Society.

“EVAR is becoming an increasingly popular strategy for treatment of AAA,” said Samer Alharthi, MD, MPH, of the University of Toledo in Ohio. “As surgeon experience and endovascular technology have improved, a greater percentage of ruptured AAA are being treated by EVAR.”

Dr. Alharthi reported on a retrospective analysis of 4,133 patients who had repair for ruptured AAA in the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Notably, the number of EVAR repairs continue to increase and peaked in 2015, with 53% of ruptured AAA treated by EVAR.

Over the term of the study, the overall mortality rate was 22.6% for EVAR and 33.2% for open repair (P less than .001), Dr. Alharthi said. “After adjusting for cofounders, there was a 41% reduction in the mortality rate with the EVAR approach,” he said.

The only appreciable significant difference in demographics between the two groups was a higher percentage of smokers with chronic obstructive pulmonary disease having open repair – 942 (49.2%) vs. 701 (36.2%) – and a higher percentage of patients with end-stage renal disease having EVAR, Dr. Alharthi said. Other comorbidities had no statistically significant difference.

“Complications – pneumonia, reintubation, and acute renal failure – were higher in the open than the EVAR group,” he said. For example, rates of acute renal failure were 15.4% and 8.2% (P less than.001), respectively. Rates of myocardial infarction were similar between the two groups: 6.3% and 6% (P = .74), respectively.

Dr. Alharthi had no financial relationships to disclose.

SOURCE: Alharthi S et al. Midwestern Vascular 2019, Abstract 13.

CHICAGO – Numerous studies have shown conflicting results for endovascular repair in ruptured abdominal aortic aneurysms (AAA), but an analysis of 4,000-plus cases from a national registry has found a 41% reduction in mortality with endovascular repair vs. open repair, according to a presentation at the annual meeting of the Midwestern Vascular Surgery Society.

“EVAR is becoming an increasingly popular strategy for treatment of AAA,” said Samer Alharthi, MD, MPH, of the University of Toledo in Ohio. “As surgeon experience and endovascular technology have improved, a greater percentage of ruptured AAA are being treated by EVAR.”

Dr. Alharthi reported on a retrospective analysis of 4,133 patients who had repair for ruptured AAA in the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Notably, the number of EVAR repairs continue to increase and peaked in 2015, with 53% of ruptured AAA treated by EVAR.

Over the term of the study, the overall mortality rate was 22.6% for EVAR and 33.2% for open repair (P less than .001), Dr. Alharthi said. “After adjusting for cofounders, there was a 41% reduction in the mortality rate with the EVAR approach,” he said.

The only appreciable significant difference in demographics between the two groups was a higher percentage of smokers with chronic obstructive pulmonary disease having open repair – 942 (49.2%) vs. 701 (36.2%) – and a higher percentage of patients with end-stage renal disease having EVAR, Dr. Alharthi said. Other comorbidities had no statistically significant difference.

“Complications – pneumonia, reintubation, and acute renal failure – were higher in the open than the EVAR group,” he said. For example, rates of acute renal failure were 15.4% and 8.2% (P less than.001), respectively. Rates of myocardial infarction were similar between the two groups: 6.3% and 6% (P = .74), respectively.

Dr. Alharthi had no financial relationships to disclose.

SOURCE: Alharthi S et al. Midwestern Vascular 2019, Abstract 13.

CHICAGO – Numerous studies have shown conflicting results for endovascular repair in ruptured abdominal aortic aneurysms (AAA), but an analysis of 4,000-plus cases from a national registry has found a 41% reduction in mortality with endovascular repair vs. open repair, according to a presentation at the annual meeting of the Midwestern Vascular Surgery Society.

“EVAR is becoming an increasingly popular strategy for treatment of AAA,” said Samer Alharthi, MD, MPH, of the University of Toledo in Ohio. “As surgeon experience and endovascular technology have improved, a greater percentage of ruptured AAA are being treated by EVAR.”

Dr. Alharthi reported on a retrospective analysis of 4,133 patients who had repair for ruptured AAA in the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Notably, the number of EVAR repairs continue to increase and peaked in 2015, with 53% of ruptured AAA treated by EVAR.

Over the term of the study, the overall mortality rate was 22.6% for EVAR and 33.2% for open repair (P less than .001), Dr. Alharthi said. “After adjusting for cofounders, there was a 41% reduction in the mortality rate with the EVAR approach,” he said.

The only appreciable significant difference in demographics between the two groups was a higher percentage of smokers with chronic obstructive pulmonary disease having open repair – 942 (49.2%) vs. 701 (36.2%) – and a higher percentage of patients with end-stage renal disease having EVAR, Dr. Alharthi said. Other comorbidities had no statistically significant difference.

“Complications – pneumonia, reintubation, and acute renal failure – were higher in the open than the EVAR group,” he said. For example, rates of acute renal failure were 15.4% and 8.2% (P less than.001), respectively. Rates of myocardial infarction were similar between the two groups: 6.3% and 6% (P = .74), respectively.

Dr. Alharthi had no financial relationships to disclose.

SOURCE: Alharthi S et al. Midwestern Vascular 2019, Abstract 13.

NEW ORLEANS – Despite guideline recommendations, ambulatory blood pressure monitoring is used for management in less than 1% of commercially insured hypertension patients in the United States, according to a University of Florida, Gainesville, analysis of claims data for almost 4 million people.

“With each iteration, evidence-based guidelines have more strongly recommended out-of-office blood pressure measurement, but it’s basically had no impact. If we are going to continue to recommend this aggressively, we need to put some pressure on both payers and providers,” said lead investigator Steven M. Smith, PharmD, of the department of pharmacotherapy & translational research, associate director of the Center for Integrative Cardiovascular and Metabolic Diseases at the university.

“A number of studies show that ambulatory blood pressure monitoring [ABPM] is more strongly predictive of outcomes than office pressure.” It’s “considered the gold standard for hypertension,” he said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension

The reason is that ABPM gives a continual reading of blood pressure over 24 hours, not just an office snapshot, and can do things that office measurements cannot, including ruling out white coat hypertension, identifying masked hypertension, and checking nocturnal dipping and morning surge, both of which are related to cardiovascular risk.

Although common in Canada and Europe, it’s no secret that ABPM hasn’t caught on in the United States. The goal of Dr. Smith’s work was to help quantify the situation.

Using Truven Health Analytics commercial insurance claims data, he and his team identified 3,378,645 adults starting their first hypertension medication and 335,200 starting their fourth from 2008 to 2017. They looked for ABPM claims in the previous 6 months as well as the month after patients started their new medication. The idea was to assess ABPM use in both new and resistant hypertensive patients.

ABPM claims were submitted for 0.15% of patients starting their first drug in 2008, rising to 0.3% in 2017. ABPM was used mostly before treatment initiation.

ABPM use actually declined among resistant patients from about 0.27% in 2008 to about 0.12% in 2017. Use was split about evenly before and after they started their fourth medication.

About 80% of claims – generally for interpreting ABPM results, not the upfront cost of the machine – were paid. Claims submitted tended to come from more high-end plans. Reimbursement rates were similar for more bargain plans, but there were many fewer claims submitted, Dr. Smith said.

He thought plans would at least follow Medicare’s reimbursement policy, which, at the time of the study, covered ABPM to rule out white coat hypertension, “but they didn’t seem to,” he said. Medicare recently added coverage for suspected masked hypertension.

The study doesn’t address why uptake is so low in the United States, but outside the world of hypertension specialists, “physicians don’t see a value in it. They don’t recognize what they would get from ABPM and how that would change what they do,” in part because treatment is currently based on office measurements. There’s also probably uncertainty about how to interpret the results, Dr. Smith said.

Standardization across payers about what they’ll cover and for whom would probably help, he added.

Findings in the study were similar for home blood pressure monitoring, but probably not an accurate gauge of use. Patients mostly buy their own devices and report the results to their physician, without getting insurance involved, he said.

There was no industry funding, and the investigators didn’t have any disclosures.

[email protected]

SOURCE: Smith SM et al. Joint Hypertension 2019, Abstract P2067.

NEW ORLEANS – Despite guideline recommendations, ambulatory blood pressure monitoring is used for management in less than 1% of commercially insured hypertension patients in the United States, according to a University of Florida, Gainesville, analysis of claims data for almost 4 million people.

“With each iteration, evidence-based guidelines have more strongly recommended out-of-office blood pressure measurement, but it’s basically had no impact. If we are going to continue to recommend this aggressively, we need to put some pressure on both payers and providers,” said lead investigator Steven M. Smith, PharmD, of the department of pharmacotherapy & translational research, associate director of the Center for Integrative Cardiovascular and Metabolic Diseases at the university.

“A number of studies show that ambulatory blood pressure monitoring [ABPM] is more strongly predictive of outcomes than office pressure.” It’s “considered the gold standard for hypertension,” he said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension

The reason is that ABPM gives a continual reading of blood pressure over 24 hours, not just an office snapshot, and can do things that office measurements cannot, including ruling out white coat hypertension, identifying masked hypertension, and checking nocturnal dipping and morning surge, both of which are related to cardiovascular risk.

Although common in Canada and Europe, it’s no secret that ABPM hasn’t caught on in the United States. The goal of Dr. Smith’s work was to help quantify the situation.

Using Truven Health Analytics commercial insurance claims data, he and his team identified 3,378,645 adults starting their first hypertension medication and 335,200 starting their fourth from 2008 to 2017. They looked for ABPM claims in the previous 6 months as well as the month after patients started their new medication. The idea was to assess ABPM use in both new and resistant hypertensive patients.

ABPM claims were submitted for 0.15% of patients starting their first drug in 2008, rising to 0.3% in 2017. ABPM was used mostly before treatment initiation.

ABPM use actually declined among resistant patients from about 0.27% in 2008 to about 0.12% in 2017. Use was split about evenly before and after they started their fourth medication.

About 80% of claims – generally for interpreting ABPM results, not the upfront cost of the machine – were paid. Claims submitted tended to come from more high-end plans. Reimbursement rates were similar for more bargain plans, but there were many fewer claims submitted, Dr. Smith said.

He thought plans would at least follow Medicare’s reimbursement policy, which, at the time of the study, covered ABPM to rule out white coat hypertension, “but they didn’t seem to,” he said. Medicare recently added coverage for suspected masked hypertension.

The study doesn’t address why uptake is so low in the United States, but outside the world of hypertension specialists, “physicians don’t see a value in it. They don’t recognize what they would get from ABPM and how that would change what they do,” in part because treatment is currently based on office measurements. There’s also probably uncertainty about how to interpret the results, Dr. Smith said.

Standardization across payers about what they’ll cover and for whom would probably help, he added.

Findings in the study were similar for home blood pressure monitoring, but probably not an accurate gauge of use. Patients mostly buy their own devices and report the results to their physician, without getting insurance involved, he said.

There was no industry funding, and the investigators didn’t have any disclosures.

[email protected]

SOURCE: Smith SM et al. Joint Hypertension 2019, Abstract P2067.

NEW ORLEANS – Despite guideline recommendations, ambulatory blood pressure monitoring is used for management in less than 1% of commercially insured hypertension patients in the United States, according to a University of Florida, Gainesville, analysis of claims data for almost 4 million people.

“With each iteration, evidence-based guidelines have more strongly recommended out-of-office blood pressure measurement, but it’s basically had no impact. If we are going to continue to recommend this aggressively, we need to put some pressure on both payers and providers,” said lead investigator Steven M. Smith, PharmD, of the department of pharmacotherapy & translational research, associate director of the Center for Integrative Cardiovascular and Metabolic Diseases at the university.

“A number of studies show that ambulatory blood pressure monitoring [ABPM] is more strongly predictive of outcomes than office pressure.” It’s “considered the gold standard for hypertension,” he said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension

The reason is that ABPM gives a continual reading of blood pressure over 24 hours, not just an office snapshot, and can do things that office measurements cannot, including ruling out white coat hypertension, identifying masked hypertension, and checking nocturnal dipping and morning surge, both of which are related to cardiovascular risk.

Although common in Canada and Europe, it’s no secret that ABPM hasn’t caught on in the United States. The goal of Dr. Smith’s work was to help quantify the situation.

Using Truven Health Analytics commercial insurance claims data, he and his team identified 3,378,645 adults starting their first hypertension medication and 335,200 starting their fourth from 2008 to 2017. They looked for ABPM claims in the previous 6 months as well as the month after patients started their new medication. The idea was to assess ABPM use in both new and resistant hypertensive patients.

ABPM claims were submitted for 0.15% of patients starting their first drug in 2008, rising to 0.3% in 2017. ABPM was used mostly before treatment initiation.

ABPM use actually declined among resistant patients from about 0.27% in 2008 to about 0.12% in 2017. Use was split about evenly before and after they started their fourth medication.

About 80% of claims – generally for interpreting ABPM results, not the upfront cost of the machine – were paid. Claims submitted tended to come from more high-end plans. Reimbursement rates were similar for more bargain plans, but there were many fewer claims submitted, Dr. Smith said.

He thought plans would at least follow Medicare’s reimbursement policy, which, at the time of the study, covered ABPM to rule out white coat hypertension, “but they didn’t seem to,” he said. Medicare recently added coverage for suspected masked hypertension.

The study doesn’t address why uptake is so low in the United States, but outside the world of hypertension specialists, “physicians don’t see a value in it. They don’t recognize what they would get from ABPM and how that would change what they do,” in part because treatment is currently based on office measurements. There’s also probably uncertainty about how to interpret the results, Dr. Smith said.

Standardization across payers about what they’ll cover and for whom would probably help, he added.

Findings in the study were similar for home blood pressure monitoring, but probably not an accurate gauge of use. Patients mostly buy their own devices and report the results to their physician, without getting insurance involved, he said.

There was no industry funding, and the investigators didn’t have any disclosures.

[email protected]

SOURCE: Smith SM et al. Joint Hypertension 2019, Abstract P2067.

ORLANDO – The use of a teleconferencing program to share knowledge about osteoporosis has helped health care professionals learn about the disease and may potentially reduce the osteoporosis treatment gap in underserved communities, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

The concept, called “technology-enabled collaborative learning,” is intended to address the problem of there being not enough specialists to see patients who need treatment, and the ineffectiveness of educating primary care providers in how to treat complex medical conditions, E. Michael Lewiecki, MD, the director of the New Mexico Clinical Research & Osteoporosis Center said in his presentation.

“Primary care doctors are busy,” said Dr. Lewiecki. “They have limited time taking care of patients. They don’t have the time or often the skills to manage patients who have any questions or concerns about osteoporosis and treatments for osteoporosis.”

One solution, he said, is to find health care professionals in underserved communities who are already interested in and motivated to learn more about osteoporosis, turn them into near-experts on osteoporosis for their patients as well as in their own community.

Dr. Lewiecki proposed the Extension for Community Healthcare Outcomes (ECHO), or Project ECHO, an initiative out of the University of New Mexico School of Medicine, as a potential answer. Project ECHO uses videoconferencing to connect experts in a therapeutic area, with Bone Health TeleECHO focusing on raising knowledge of osteoporosis for its participants. “The idea of ECHO is to be a force multiplier to educate health care professionals, each of whom takes care of many patients, and to have many ECHO programs around the world in convenient time zones and convenient languages for people who are interested in participating,” said Dr. Lewiecki.

The idea began when a gastroenterologist at Dr. Lewiecki’s own center was frustrated that patients were not seeking treatment for hepatitis C because of time or travel issues. In response, a pilot program for Project ECHO was developed through a collaboration between the University of New Mexico Health Sciences Center and the Osteoporosis Foundation of New Mexico where gastroenterologists at University of New Mexico connected with primary care providers across the state, sharing information about hepatitis C and discussing case studies. The results of the pilot program were published in the New England Journal of Medicine and showed a similar rate of sustained viral response between patients treated at the University of New Mexico clinic (84 of 146 patients; 57.5%) and at 21 ECHO clinics (152 of 261 patients; 58.2%) (Arora S et al. N Eng J Med. 2011. doi: 10.1056/NEJMoa1009370).

“ECHO expands the capacity to deliver best practice medical care through collegial, interactive, case-based discussions with minimal disruption to the office routine,” said Dr. Lewiecki. “Patients benefit from better care, closer to home, with greater convenience and lower cost than referral to a medical center. And the potential is to reduce the osteoporosis treatment gap by having many ECHOs starting up in many places in the world.”

Today, the ECHO program is in 37 countries, with 322 ECHO hubs and 677 ECHO programs. The top three specialties are endocrinology, orthopedics, and rheumatology; 51% of ECHO participants are primary care providers, 24% are advanced care providers, and 19% are health care providers such as nutritionists, physical therapists, and other providers that have an interest in bone health.

In survey results adapted from a 2017 study from his own group, Dr. Lewiecki showed that 263 health care professionals who participated in Bone Health TeleECHO rated themselves as more confident in 20 different domains of osteoporosis treatment, such as secondary osteoporosis and anabolic therapy, after 21 months of using the ECHO program (Lewiecki EM et al. J Endocr Soc. 2017. doi: 10.1210/js.2017-00361). However, he admitted that showing fracture prevention outcomes at these ECHO centers has proven more difficult.

“Of course, we’re all interested in outcomes. The ultimate outcome here is preventing fractures, but it is extraordinarily difficult to design a study to actually show that we’re reducing fractures, but certainly self-confidence in managing osteoporosis has improved,” he said.

There have also been some misconceptions of the Project ECHO. The program is not only for beginners or primary care providers, said Dr. Lewiecki. It is also not limited to providers in rural areas, as the program has many participants at urban centers, he added.

“We are a virtual community of practice. It’s a collegial relationship,” he said. “It’s really recapitulating the way that we learned during our postgraduate training: When we see a patient, we present the case to our attending, the attending pontificates a little bit, we bounce things off of one another, and we go back and then we do some different things with our patients. And that’s exactly what we do with Echo. It makes learning fun again.”

Dr. Lewiecki challenged the attendees in the room who are already experts in osteoporosis to help share their knowledge of the disease to help other health care professionals learn more about how to better care for their patients. “If you have a passion for teaching, if you want to share knowledge and you’re willing to devote a little bit of your time to doing that and reaching out to more people, this is the way that you can do it.”

Dr. Lewiecki reports research grant support from Amgen, consulting fees from Alexion, Amgen, Radius, Shire, and Ultragenyx, speaking fees from Alexion, Radius, and Shire, and is an advisory board member with the National Osteoporosis Foundation, International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico.

SOURCE: Lewiecki ME. ASBMR 2019. Symposia: Cutting Edge Concepts: Novel Approaches to Reducing Fractures. Bone Health TeleECHO.

ORLANDO – The use of a teleconferencing program to share knowledge about osteoporosis has helped health care professionals learn about the disease and may potentially reduce the osteoporosis treatment gap in underserved communities, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

The concept, called “technology-enabled collaborative learning,” is intended to address the problem of there being not enough specialists to see patients who need treatment, and the ineffectiveness of educating primary care providers in how to treat complex medical conditions, E. Michael Lewiecki, MD, the director of the New Mexico Clinical Research & Osteoporosis Center said in his presentation.

“Primary care doctors are busy,” said Dr. Lewiecki. “They have limited time taking care of patients. They don’t have the time or often the skills to manage patients who have any questions or concerns about osteoporosis and treatments for osteoporosis.”

One solution, he said, is to find health care professionals in underserved communities who are already interested in and motivated to learn more about osteoporosis, turn them into near-experts on osteoporosis for their patients as well as in their own community.

Dr. Lewiecki proposed the Extension for Community Healthcare Outcomes (ECHO), or Project ECHO, an initiative out of the University of New Mexico School of Medicine, as a potential answer. Project ECHO uses videoconferencing to connect experts in a therapeutic area, with Bone Health TeleECHO focusing on raising knowledge of osteoporosis for its participants. “The idea of ECHO is to be a force multiplier to educate health care professionals, each of whom takes care of many patients, and to have many ECHO programs around the world in convenient time zones and convenient languages for people who are interested in participating,” said Dr. Lewiecki.

The idea began when a gastroenterologist at Dr. Lewiecki’s own center was frustrated that patients were not seeking treatment for hepatitis C because of time or travel issues. In response, a pilot program for Project ECHO was developed through a collaboration between the University of New Mexico Health Sciences Center and the Osteoporosis Foundation of New Mexico where gastroenterologists at University of New Mexico connected with primary care providers across the state, sharing information about hepatitis C and discussing case studies. The results of the pilot program were published in the New England Journal of Medicine and showed a similar rate of sustained viral response between patients treated at the University of New Mexico clinic (84 of 146 patients; 57.5%) and at 21 ECHO clinics (152 of 261 patients; 58.2%) (Arora S et al. N Eng J Med. 2011. doi: 10.1056/NEJMoa1009370).

“ECHO expands the capacity to deliver best practice medical care through collegial, interactive, case-based discussions with minimal disruption to the office routine,” said Dr. Lewiecki. “Patients benefit from better care, closer to home, with greater convenience and lower cost than referral to a medical center. And the potential is to reduce the osteoporosis treatment gap by having many ECHOs starting up in many places in the world.”

Today, the ECHO program is in 37 countries, with 322 ECHO hubs and 677 ECHO programs. The top three specialties are endocrinology, orthopedics, and rheumatology; 51% of ECHO participants are primary care providers, 24% are advanced care providers, and 19% are health care providers such as nutritionists, physical therapists, and other providers that have an interest in bone health.

In survey results adapted from a 2017 study from his own group, Dr. Lewiecki showed that 263 health care professionals who participated in Bone Health TeleECHO rated themselves as more confident in 20 different domains of osteoporosis treatment, such as secondary osteoporosis and anabolic therapy, after 21 months of using the ECHO program (Lewiecki EM et al. J Endocr Soc. 2017. doi: 10.1210/js.2017-00361). However, he admitted that showing fracture prevention outcomes at these ECHO centers has proven more difficult.

“Of course, we’re all interested in outcomes. The ultimate outcome here is preventing fractures, but it is extraordinarily difficult to design a study to actually show that we’re reducing fractures, but certainly self-confidence in managing osteoporosis has improved,” he said.

There have also been some misconceptions of the Project ECHO. The program is not only for beginners or primary care providers, said Dr. Lewiecki. It is also not limited to providers in rural areas, as the program has many participants at urban centers, he added.

“We are a virtual community of practice. It’s a collegial relationship,” he said. “It’s really recapitulating the way that we learned during our postgraduate training: When we see a patient, we present the case to our attending, the attending pontificates a little bit, we bounce things off of one another, and we go back and then we do some different things with our patients. And that’s exactly what we do with Echo. It makes learning fun again.”

Dr. Lewiecki challenged the attendees in the room who are already experts in osteoporosis to help share their knowledge of the disease to help other health care professionals learn more about how to better care for their patients. “If you have a passion for teaching, if you want to share knowledge and you’re willing to devote a little bit of your time to doing that and reaching out to more people, this is the way that you can do it.”

Dr. Lewiecki reports research grant support from Amgen, consulting fees from Alexion, Amgen, Radius, Shire, and Ultragenyx, speaking fees from Alexion, Radius, and Shire, and is an advisory board member with the National Osteoporosis Foundation, International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico.

SOURCE: Lewiecki ME. ASBMR 2019. Symposia: Cutting Edge Concepts: Novel Approaches to Reducing Fractures. Bone Health TeleECHO.

ORLANDO – The use of a teleconferencing program to share knowledge about osteoporosis has helped health care professionals learn about the disease and may potentially reduce the osteoporosis treatment gap in underserved communities, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

The concept, called “technology-enabled collaborative learning,” is intended to address the problem of there being not enough specialists to see patients who need treatment, and the ineffectiveness of educating primary care providers in how to treat complex medical conditions, E. Michael Lewiecki, MD, the director of the New Mexico Clinical Research & Osteoporosis Center said in his presentation.

“Primary care doctors are busy,” said Dr. Lewiecki. “They have limited time taking care of patients. They don’t have the time or often the skills to manage patients who have any questions or concerns about osteoporosis and treatments for osteoporosis.”

One solution, he said, is to find health care professionals in underserved communities who are already interested in and motivated to learn more about osteoporosis, turn them into near-experts on osteoporosis for their patients as well as in their own community.

Dr. Lewiecki proposed the Extension for Community Healthcare Outcomes (ECHO), or Project ECHO, an initiative out of the University of New Mexico School of Medicine, as a potential answer. Project ECHO uses videoconferencing to connect experts in a therapeutic area, with Bone Health TeleECHO focusing on raising knowledge of osteoporosis for its participants. “The idea of ECHO is to be a force multiplier to educate health care professionals, each of whom takes care of many patients, and to have many ECHO programs around the world in convenient time zones and convenient languages for people who are interested in participating,” said Dr. Lewiecki.

The idea began when a gastroenterologist at Dr. Lewiecki’s own center was frustrated that patients were not seeking treatment for hepatitis C because of time or travel issues. In response, a pilot program for Project ECHO was developed through a collaboration between the University of New Mexico Health Sciences Center and the Osteoporosis Foundation of New Mexico where gastroenterologists at University of New Mexico connected with primary care providers across the state, sharing information about hepatitis C and discussing case studies. The results of the pilot program were published in the New England Journal of Medicine and showed a similar rate of sustained viral response between patients treated at the University of New Mexico clinic (84 of 146 patients; 57.5%) and at 21 ECHO clinics (152 of 261 patients; 58.2%) (Arora S et al. N Eng J Med. 2011. doi: 10.1056/NEJMoa1009370).

“ECHO expands the capacity to deliver best practice medical care through collegial, interactive, case-based discussions with minimal disruption to the office routine,” said Dr. Lewiecki. “Patients benefit from better care, closer to home, with greater convenience and lower cost than referral to a medical center. And the potential is to reduce the osteoporosis treatment gap by having many ECHOs starting up in many places in the world.”

Today, the ECHO program is in 37 countries, with 322 ECHO hubs and 677 ECHO programs. The top three specialties are endocrinology, orthopedics, and rheumatology; 51% of ECHO participants are primary care providers, 24% are advanced care providers, and 19% are health care providers such as nutritionists, physical therapists, and other providers that have an interest in bone health.

In survey results adapted from a 2017 study from his own group, Dr. Lewiecki showed that 263 health care professionals who participated in Bone Health TeleECHO rated themselves as more confident in 20 different domains of osteoporosis treatment, such as secondary osteoporosis and anabolic therapy, after 21 months of using the ECHO program (Lewiecki EM et al. J Endocr Soc. 2017. doi: 10.1210/js.2017-00361). However, he admitted that showing fracture prevention outcomes at these ECHO centers has proven more difficult.

“Of course, we’re all interested in outcomes. The ultimate outcome here is preventing fractures, but it is extraordinarily difficult to design a study to actually show that we’re reducing fractures, but certainly self-confidence in managing osteoporosis has improved,” he said.

There have also been some misconceptions of the Project ECHO. The program is not only for beginners or primary care providers, said Dr. Lewiecki. It is also not limited to providers in rural areas, as the program has many participants at urban centers, he added.

“We are a virtual community of practice. It’s a collegial relationship,” he said. “It’s really recapitulating the way that we learned during our postgraduate training: When we see a patient, we present the case to our attending, the attending pontificates a little bit, we bounce things off of one another, and we go back and then we do some different things with our patients. And that’s exactly what we do with Echo. It makes learning fun again.”

Dr. Lewiecki challenged the attendees in the room who are already experts in osteoporosis to help share their knowledge of the disease to help other health care professionals learn more about how to better care for their patients. “If you have a passion for teaching, if you want to share knowledge and you’re willing to devote a little bit of your time to doing that and reaching out to more people, this is the way that you can do it.”

Dr. Lewiecki reports research grant support from Amgen, consulting fees from Alexion, Amgen, Radius, Shire, and Ultragenyx, speaking fees from Alexion, Radius, and Shire, and is an advisory board member with the National Osteoporosis Foundation, International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico.

SOURCE: Lewiecki ME. ASBMR 2019. Symposia: Cutting Edge Concepts: Novel Approaches to Reducing Fractures. Bone Health TeleECHO.

Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.

Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.

“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”

The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.

The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).

“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”

They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.

The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.

[email protected]

SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.

Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.

Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.

“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”

The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.

The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).

“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”

They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.

The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.

[email protected]

SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.

Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.

Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.

“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”

The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.

The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).

“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”

They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.

The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.

[email protected]

SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.

SAN DIEGO – In the coming years, expect to see an increasing number of neuromodulators hit the market, Joel L. Cohen, MD, predicted at the annual Masters of Aesthetics Symposium.

One such product, DaxibotulinumtoxinA (Daxi), formerly known as RT002, contains a proprietary peptide that may contribute to extending its duration of action beyond currently available neuromodulator products. “Another difference for Daxi is that it does not contain human serum albumin,” said Dr. Cohen, who’s in private practice in Greenwood Village and Lone Tree, both in Colo.

In trials of the agent conducted by Revance, the manufacturer, for the treatment of moderate to severe glabellar lines, DaxibotulinumtoxinA achieved a 1-point change in results from baseline in a median of 24 weeks, while the return to baseline wrinkle severity occurred in a median of 28 weeks. According to the Revance web site, DaxibotulinumtoxinA is up for possible Food and Drug Administration approval in 2020.

Though current neuromodulators on the market may be most effective for 3-4 months, the reality is that patients often don’t come in for longer stretches of time – as there is still some degree of efficacy. Dr. Cohen shared interim data from an ongoing study that showed that at 6 months 69% of patients remain satisfied with the result of their last injection. “With Dysport, for example, even though we know the durability is to 3-4 months, we have patients who may still be happy with the results at 6 months,” he said.

Another trend he discussed is the increasing interest in QM1114, a novel, ready-to-use type A botulinum toxin formulation being developed by Galderma for the aesthetic treatment of glabellar lines. Unlike Botox, Dysport, Xeomin, and Jueveau, QM1114 is a liquid and thus does not require reconstitution.

“Myobloc is also a liquid but it is a type B botulinum toxin,” Dr. Cohen said. “It’s always been formulated as a liquid toxin, but it’s not something we can use commonly in our aesthetic practices [unless a patient is suspected of having extremely rare type A antibodies] for many reasons beyond simply it not being approved for aesthetic use. Though Myobloc kicks in faster, it spreads more, it hurts more, and it doesn’t last as long.”

In a phase 2 study presented at the 2019 World Congress of Dermatology, investigators, including Dr. Cohen, evaluated the safety and efficacy of QM1114 for the treatment of glabellar lines in 359 patients aged 23-79 years. Patients were randomly assigned to one of three single-treatment groups – 35 units, 45 units, or 60 units – or to placebo. Two weeks post treatment, wrinkle severity improved by at least two grades based on the assessment of investigators (a range from 83%-91%) and by that of treated subjects (a range from 73%-86%), compared with 6% and 8%, respectively, in the placebo group. In addition, 90%-98% of subjects rated themselves as “very satisfied” or “satisfied” with the treatment at month 1, compared with 72%-80% of subjects at month 6. Treatment-related adverse events occurred in little more than 1% of subjects in any QM1114 group and presented as mild to moderate injection-site pain, headache, eyelid ptosis, injection-site pruritus, injection-site swelling, and eyelid edema.

Dr. Cohen reported having research and financial ties to numerous pharmaceutical and device companies including Merz, Galderma, Allergan, Revance, Evolus, and Croma.

[email protected]

SAN DIEGO – In the coming years, expect to see an increasing number of neuromodulators hit the market, Joel L. Cohen, MD, predicted at the annual Masters of Aesthetics Symposium.

One such product, DaxibotulinumtoxinA (Daxi), formerly known as RT002, contains a proprietary peptide that may contribute to extending its duration of action beyond currently available neuromodulator products. “Another difference for Daxi is that it does not contain human serum albumin,” said Dr. Cohen, who’s in private practice in Greenwood Village and Lone Tree, both in Colo.

In trials of the agent conducted by Revance, the manufacturer, for the treatment of moderate to severe glabellar lines, DaxibotulinumtoxinA achieved a 1-point change in results from baseline in a median of 24 weeks, while the return to baseline wrinkle severity occurred in a median of 28 weeks. According to the Revance web site, DaxibotulinumtoxinA is up for possible Food and Drug Administration approval in 2020.

Though current neuromodulators on the market may be most effective for 3-4 months, the reality is that patients often don’t come in for longer stretches of time – as there is still some degree of efficacy. Dr. Cohen shared interim data from an ongoing study that showed that at 6 months 69% of patients remain satisfied with the result of their last injection. “With Dysport, for example, even though we know the durability is to 3-4 months, we have patients who may still be happy with the results at 6 months,” he said.

Another trend he discussed is the increasing interest in QM1114, a novel, ready-to-use type A botulinum toxin formulation being developed by Galderma for the aesthetic treatment of glabellar lines. Unlike Botox, Dysport, Xeomin, and Jueveau, QM1114 is a liquid and thus does not require reconstitution.

“Myobloc is also a liquid but it is a type B botulinum toxin,” Dr. Cohen said. “It’s always been formulated as a liquid toxin, but it’s not something we can use commonly in our aesthetic practices [unless a patient is suspected of having extremely rare type A antibodies] for many reasons beyond simply it not being approved for aesthetic use. Though Myobloc kicks in faster, it spreads more, it hurts more, and it doesn’t last as long.”

In a phase 2 study presented at the 2019 World Congress of Dermatology, investigators, including Dr. Cohen, evaluated the safety and efficacy of QM1114 for the treatment of glabellar lines in 359 patients aged 23-79 years. Patients were randomly assigned to one of three single-treatment groups – 35 units, 45 units, or 60 units – or to placebo. Two weeks post treatment, wrinkle severity improved by at least two grades based on the assessment of investigators (a range from 83%-91%) and by that of treated subjects (a range from 73%-86%), compared with 6% and 8%, respectively, in the placebo group. In addition, 90%-98% of subjects rated themselves as “very satisfied” or “satisfied” with the treatment at month 1, compared with 72%-80% of subjects at month 6. Treatment-related adverse events occurred in little more than 1% of subjects in any QM1114 group and presented as mild to moderate injection-site pain, headache, eyelid ptosis, injection-site pruritus, injection-site swelling, and eyelid edema.

Dr. Cohen reported having research and financial ties to numerous pharmaceutical and device companies including Merz, Galderma, Allergan, Revance, Evolus, and Croma.

[email protected]

SAN DIEGO – In the coming years, expect to see an increasing number of neuromodulators hit the market, Joel L. Cohen, MD, predicted at the annual Masters of Aesthetics Symposium.

One such product, DaxibotulinumtoxinA (Daxi), formerly known as RT002, contains a proprietary peptide that may contribute to extending its duration of action beyond currently available neuromodulator products. “Another difference for Daxi is that it does not contain human serum albumin,” said Dr. Cohen, who’s in private practice in Greenwood Village and Lone Tree, both in Colo.

In trials of the agent conducted by Revance, the manufacturer, for the treatment of moderate to severe glabellar lines, DaxibotulinumtoxinA achieved a 1-point change in results from baseline in a median of 24 weeks, while the return to baseline wrinkle severity occurred in a median of 28 weeks. According to the Revance web site, DaxibotulinumtoxinA is up for possible Food and Drug Administration approval in 2020.

Though current neuromodulators on the market may be most effective for 3-4 months, the reality is that patients often don’t come in for longer stretches of time – as there is still some degree of efficacy. Dr. Cohen shared interim data from an ongoing study that showed that at 6 months 69% of patients remain satisfied with the result of their last injection. “With Dysport, for example, even though we know the durability is to 3-4 months, we have patients who may still be happy with the results at 6 months,” he said.

Another trend he discussed is the increasing interest in QM1114, a novel, ready-to-use type A botulinum toxin formulation being developed by Galderma for the aesthetic treatment of glabellar lines. Unlike Botox, Dysport, Xeomin, and Jueveau, QM1114 is a liquid and thus does not require reconstitution.

“Myobloc is also a liquid but it is a type B botulinum toxin,” Dr. Cohen said. “It’s always been formulated as a liquid toxin, but it’s not something we can use commonly in our aesthetic practices [unless a patient is suspected of having extremely rare type A antibodies] for many reasons beyond simply it not being approved for aesthetic use. Though Myobloc kicks in faster, it spreads more, it hurts more, and it doesn’t last as long.”

In a phase 2 study presented at the 2019 World Congress of Dermatology, investigators, including Dr. Cohen, evaluated the safety and efficacy of QM1114 for the treatment of glabellar lines in 359 patients aged 23-79 years. Patients were randomly assigned to one of three single-treatment groups – 35 units, 45 units, or 60 units – or to placebo. Two weeks post treatment, wrinkle severity improved by at least two grades based on the assessment of investigators (a range from 83%-91%) and by that of treated subjects (a range from 73%-86%), compared with 6% and 8%, respectively, in the placebo group. In addition, 90%-98% of subjects rated themselves as “very satisfied” or “satisfied” with the treatment at month 1, compared with 72%-80% of subjects at month 6. Treatment-related adverse events occurred in little more than 1% of subjects in any QM1114 group and presented as mild to moderate injection-site pain, headache, eyelid ptosis, injection-site pruritus, injection-site swelling, and eyelid edema.

Dr. Cohen reported having research and financial ties to numerous pharmaceutical and device companies including Merz, Galderma, Allergan, Revance, Evolus, and Croma.

[email protected]

BARCELONA – The glucagonlike peptide–1 receptor antagonist semaglutide (Ozempic) produced greater reductions in glycated hemoglobin and body weight than the sodium-glucose cotransporter 2 inhibitor canagliflozin (Invokana) in second-line treatment in patients with type 2 diabetes after metformin and lifestyle modifications, researchers reported at the annual meeting of the European Association for the Study of Diabetes.

The year-long SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) 8 trial comparing semaglutide and canagliflozin is one of the few head-to-head comparisons of the glucagonlike peptide–1 receptor antagonist (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitor classes of drugs.

Findings showed overall changes in HbA_{1c level} from baseline to week 52 of –1.5 percentage points with semaglutide and –1.0 percentage point with canagliflozin, and changes in body weight during the same time of –5.3 kg and –4.2 kg, respectively. The estimated treatment differences were –0.49 percentage points for HbA_1c (P less than .001) and –1.06 kg for body weight (P less than .0029).

A significantly higher percentage of patients receiving semaglutide also achieved HbA_1c targets at 52 weeks, compared with those receiving canagliflozin: 66.1% versus 45.1%, respectively, achieved the American Diabetes Association’s target of less than 7%, and 52.8% versus 23.6% (P less than .0001) reached the lower target of 6.5% or lower, as set by the American Association of Clinical Endocrinologists.

Furthermore, a significantly higher proportion of patients in the semaglutide arm achieved 10% or more weight loss by the end of the study (22.3% vs. 8.9% in the canagliflozin arm; P less than .0001), with a trend for 5% or greater weight loss favoring semaglutide (51.1% vs. 46.6%, P = .21). A post hoc analysis also showed that patients treated with semaglutide could achieve a weight loss of 15% or more (6.8% vs. 0.9% for canagliflozin, P = .0001).

“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes [of drugs] as second-line therapy in patients with type 2 diabetes,” lead study author Ildiko Lingvay, MD, said. The findings support the use of semaglutide as an alternative to canagliflozin when treatment intensification after metformin is needed, Dr. Lingvay and coauthors concluded in an article published simultaneously in Lancet Diabetes & Endocrinology (2019 Sep 17. doi: 10.1016/S2213-8587[19]30311-0).

Dr. Lingvay of the University of Texas in Dallas observed that both GLP-1 RAs and SGLT2 inhibitors are recommended as second-line treatment after metformin and lifestyle modifications, particularly when there is a need to minimize the risk for hypoglycemia and weight gain, and there is established cardiovascular disease. Despite their wide endorsement, however, there has really been only one other head-to-head trial that evaluated the two drug classes – the PIONEER 2 study, which compared oral semaglutide and the SGLT2 inhibitor empagliflozin (Jardiance). Another trial, DURATION-8, compared the GLP-1 RA exenatide (Byetta) or the SGLT2 inhibitor dapagliflozin (Farxiga) with an exenatide-dapagliflozin combination, but it did not directly compare the two drug classes.

SUSTAIN 8 was a phase 3b, randomized, double-blind, parallel-group, controlled trial that compared once-weekly subcutaneous semaglutide 1.0 mg and daily oral canagliflozin 300 mg as add-on treatments to metformin in 788 individuals with type 2 diabetes. Participants had to have a starting HbA_1c of between 7.0% and 10.0%, to be on a stable dose of metformin, and to have an estimated glomerular filtration rate of 60 mL/min per 1.73 m³ or higher.

Of the 394 patients randomized to semaglutide, 83.3% completed the study treatment and 15.7% discontinued prematurely, most often because of adverse events (9.7%). Of the remaining 394 patients randomized to canagliflozin therapy, 87.1% completed treatment and 12.9% discontinued prematurely, again mostly for adverse events (5.1%).

Overall the rate of any adverse events (76.0% vs. 71.8%) or serious adverse events (4.6% vs. 5.3%) were similar between the semaglutide and canagliflozin groups. As expected, more gastrointestinal side effects were seen in patients treated with semaglutide than in those treated with canagliflozin (46.9% vs. 27.9%), and there were more infections in the canagliflozin group (29.1% vs. 34.5%). Hypoglycemic episodes were “very rare in this population,” Dr. Lingvay reported. Rates of severe or confirmed hypoglycemia were 1.5% and 1.3% for the respective arms.

Other findings of note were improved fasting blood lipids – with greater changes in total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides seen with semaglutide than canagliflozin. Systolic blood pressure dropped in both groups, with a greater change in the canagliflozin than semaglutide group (–5.5 mm Hg vs. –3.5 mm Hg; P = .0452).

In a substudy of SUSTAIN 8 (n = 178), which was reported separately at the meeting, both semaglutide and canagliflozin reduced total fat mass as assessed with whole-body, dual-energy x-ray absorptiometry scanning. The changes in total fat mass from baseline to week 52 were a respective –3.4 kg and –2.6, or 1.4% and 1.2%. Total lean mass changed by a respective –2.3 kg and –1.5 kg (1.2% and 1.1%), and visceral fat mass by –0.2 kg and –0.1 kg (–0.9% and 0.4%). There was no statistical significance between the groups. A post hoc analysis did show, however, that a greater drop in waist circumference might be achieved with semaglutide than with canagliflozin (–4.0 vs. –2.9 cm [–3.9% vs. –2.5%], P = .02).

“Importantly, neither treatment was associated with deleterious body composition changes, such as gains in fat mass or reductions in the total lean mass,” said Rory McCrimmon, MBChB, professor of experimental diabetes and metabolism at the University of Dundee, Scotland, when presenting the substudy findings.

“These findings are consistent with results from other body composition studies with GLP-1 RAs and SGLT2 [inhibitors],”Dr. McCrimmon said, adding that “the positive effects on total fat loss and visceral fat reduction highlight the role of semaglutide and canagliflozin as relevant treatment options for patients with type 2 diabetes.”

Novo Nordisk funded the study. Dr. Lingvay has received consulting fees from Novo Nordisk; research grants from her institution; and grants, personal fees, or both, from other companies not related to the study. Dr. McCrimmon has received personal fees from Novo Nordisk and two other companies.
 

SOURCES: Lingvay I et al. Lancet Diabetes Endocrinol. 2019 Sep 17. doi: 10.1016/S2213-8587(19)30311-0; McCrimmon RJ et al. EASD 2019, Abstract 54.

BARCELONA – The glucagonlike peptide–1 receptor antagonist semaglutide (Ozempic) produced greater reductions in glycated hemoglobin and body weight than the sodium-glucose cotransporter 2 inhibitor canagliflozin (Invokana) in second-line treatment in patients with type 2 diabetes after metformin and lifestyle modifications, researchers reported at the annual meeting of the European Association for the Study of Diabetes.

The year-long SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) 8 trial comparing semaglutide and canagliflozin is one of the few head-to-head comparisons of the glucagonlike peptide–1 receptor antagonist (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitor classes of drugs.

Findings showed overall changes in HbA_{1c level} from baseline to week 52 of –1.5 percentage points with semaglutide and –1.0 percentage point with canagliflozin, and changes in body weight during the same time of –5.3 kg and –4.2 kg, respectively. The estimated treatment differences were –0.49 percentage points for HbA_1c (P less than .001) and –1.06 kg for body weight (P less than .0029).

A significantly higher percentage of patients receiving semaglutide also achieved HbA_1c targets at 52 weeks, compared with those receiving canagliflozin: 66.1% versus 45.1%, respectively, achieved the American Diabetes Association’s target of less than 7%, and 52.8% versus 23.6% (P less than .0001) reached the lower target of 6.5% or lower, as set by the American Association of Clinical Endocrinologists.

Furthermore, a significantly higher proportion of patients in the semaglutide arm achieved 10% or more weight loss by the end of the study (22.3% vs. 8.9% in the canagliflozin arm; P less than .0001), with a trend for 5% or greater weight loss favoring semaglutide (51.1% vs. 46.6%, P = .21). A post hoc analysis also showed that patients treated with semaglutide could achieve a weight loss of 15% or more (6.8% vs. 0.9% for canagliflozin, P = .0001).

“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes [of drugs] as second-line therapy in patients with type 2 diabetes,” lead study author Ildiko Lingvay, MD, said. The findings support the use of semaglutide as an alternative to canagliflozin when treatment intensification after metformin is needed, Dr. Lingvay and coauthors concluded in an article published simultaneously in Lancet Diabetes & Endocrinology (2019 Sep 17. doi: 10.1016/S2213-8587[19]30311-0).

Dr. Lingvay of the University of Texas in Dallas observed that both GLP-1 RAs and SGLT2 inhibitors are recommended as second-line treatment after metformin and lifestyle modifications, particularly when there is a need to minimize the risk for hypoglycemia and weight gain, and there is established cardiovascular disease. Despite their wide endorsement, however, there has really been only one other head-to-head trial that evaluated the two drug classes – the PIONEER 2 study, which compared oral semaglutide and the SGLT2 inhibitor empagliflozin (Jardiance). Another trial, DURATION-8, compared the GLP-1 RA exenatide (Byetta) or the SGLT2 inhibitor dapagliflozin (Farxiga) with an exenatide-dapagliflozin combination, but it did not directly compare the two drug classes.

SUSTAIN 8 was a phase 3b, randomized, double-blind, parallel-group, controlled trial that compared once-weekly subcutaneous semaglutide 1.0 mg and daily oral canagliflozin 300 mg as add-on treatments to metformin in 788 individuals with type 2 diabetes. Participants had to have a starting HbA_1c of between 7.0% and 10.0%, to be on a stable dose of metformin, and to have an estimated glomerular filtration rate of 60 mL/min per 1.73 m³ or higher.

Of the 394 patients randomized to semaglutide, 83.3% completed the study treatment and 15.7% discontinued prematurely, most often because of adverse events (9.7%). Of the remaining 394 patients randomized to canagliflozin therapy, 87.1% completed treatment and 12.9% discontinued prematurely, again mostly for adverse events (5.1%).

Overall the rate of any adverse events (76.0% vs. 71.8%) or serious adverse events (4.6% vs. 5.3%) were similar between the semaglutide and canagliflozin groups. As expected, more gastrointestinal side effects were seen in patients treated with semaglutide than in those treated with canagliflozin (46.9% vs. 27.9%), and there were more infections in the canagliflozin group (29.1% vs. 34.5%). Hypoglycemic episodes were “very rare in this population,” Dr. Lingvay reported. Rates of severe or confirmed hypoglycemia were 1.5% and 1.3% for the respective arms.

Other findings of note were improved fasting blood lipids – with greater changes in total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides seen with semaglutide than canagliflozin. Systolic blood pressure dropped in both groups, with a greater change in the canagliflozin than semaglutide group (–5.5 mm Hg vs. –3.5 mm Hg; P = .0452).

In a substudy of SUSTAIN 8 (n = 178), which was reported separately at the meeting, both semaglutide and canagliflozin reduced total fat mass as assessed with whole-body, dual-energy x-ray absorptiometry scanning. The changes in total fat mass from baseline to week 52 were a respective –3.4 kg and –2.6, or 1.4% and 1.2%. Total lean mass changed by a respective –2.3 kg and –1.5 kg (1.2% and 1.1%), and visceral fat mass by –0.2 kg and –0.1 kg (–0.9% and 0.4%). There was no statistical significance between the groups. A post hoc analysis did show, however, that a greater drop in waist circumference might be achieved with semaglutide than with canagliflozin (–4.0 vs. –2.9 cm [–3.9% vs. –2.5%], P = .02).

“Importantly, neither treatment was associated with deleterious body composition changes, such as gains in fat mass or reductions in the total lean mass,” said Rory McCrimmon, MBChB, professor of experimental diabetes and metabolism at the University of Dundee, Scotland, when presenting the substudy findings.

“These findings are consistent with results from other body composition studies with GLP-1 RAs and SGLT2 [inhibitors],”Dr. McCrimmon said, adding that “the positive effects on total fat loss and visceral fat reduction highlight the role of semaglutide and canagliflozin as relevant treatment options for patients with type 2 diabetes.”

Novo Nordisk funded the study. Dr. Lingvay has received consulting fees from Novo Nordisk; research grants from her institution; and grants, personal fees, or both, from other companies not related to the study. Dr. McCrimmon has received personal fees from Novo Nordisk and two other companies.
 

SOURCES: Lingvay I et al. Lancet Diabetes Endocrinol. 2019 Sep 17. doi: 10.1016/S2213-8587(19)30311-0; McCrimmon RJ et al. EASD 2019, Abstract 54.

BARCELONA – The glucagonlike peptide–1 receptor antagonist semaglutide (Ozempic) produced greater reductions in glycated hemoglobin and body weight than the sodium-glucose cotransporter 2 inhibitor canagliflozin (Invokana) in second-line treatment in patients with type 2 diabetes after metformin and lifestyle modifications, researchers reported at the annual meeting of the European Association for the Study of Diabetes.

The year-long SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) 8 trial comparing semaglutide and canagliflozin is one of the few head-to-head comparisons of the glucagonlike peptide–1 receptor antagonist (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitor classes of drugs.

Findings showed overall changes in HbA_{1c level} from baseline to week 52 of –1.5 percentage points with semaglutide and –1.0 percentage point with canagliflozin, and changes in body weight during the same time of –5.3 kg and –4.2 kg, respectively. The estimated treatment differences were –0.49 percentage points for HbA_1c (P less than .001) and –1.06 kg for body weight (P less than .0029).

A significantly higher percentage of patients receiving semaglutide also achieved HbA_1c targets at 52 weeks, compared with those receiving canagliflozin: 66.1% versus 45.1%, respectively, achieved the American Diabetes Association’s target of less than 7%, and 52.8% versus 23.6% (P less than .0001) reached the lower target of 6.5% or lower, as set by the American Association of Clinical Endocrinologists.

Furthermore, a significantly higher proportion of patients in the semaglutide arm achieved 10% or more weight loss by the end of the study (22.3% vs. 8.9% in the canagliflozin arm; P less than .0001), with a trend for 5% or greater weight loss favoring semaglutide (51.1% vs. 46.6%, P = .21). A post hoc analysis also showed that patients treated with semaglutide could achieve a weight loss of 15% or more (6.8% vs. 0.9% for canagliflozin, P = .0001).

“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes [of drugs] as second-line therapy in patients with type 2 diabetes,” lead study author Ildiko Lingvay, MD, said. The findings support the use of semaglutide as an alternative to canagliflozin when treatment intensification after metformin is needed, Dr. Lingvay and coauthors concluded in an article published simultaneously in Lancet Diabetes & Endocrinology (2019 Sep 17. doi: 10.1016/S2213-8587[19]30311-0).

Dr. Lingvay of the University of Texas in Dallas observed that both GLP-1 RAs and SGLT2 inhibitors are recommended as second-line treatment after metformin and lifestyle modifications, particularly when there is a need to minimize the risk for hypoglycemia and weight gain, and there is established cardiovascular disease. Despite their wide endorsement, however, there has really been only one other head-to-head trial that evaluated the two drug classes – the PIONEER 2 study, which compared oral semaglutide and the SGLT2 inhibitor empagliflozin (Jardiance). Another trial, DURATION-8, compared the GLP-1 RA exenatide (Byetta) or the SGLT2 inhibitor dapagliflozin (Farxiga) with an exenatide-dapagliflozin combination, but it did not directly compare the two drug classes.

SUSTAIN 8 was a phase 3b, randomized, double-blind, parallel-group, controlled trial that compared once-weekly subcutaneous semaglutide 1.0 mg and daily oral canagliflozin 300 mg as add-on treatments to metformin in 788 individuals with type 2 diabetes. Participants had to have a starting HbA_1c of between 7.0% and 10.0%, to be on a stable dose of metformin, and to have an estimated glomerular filtration rate of 60 mL/min per 1.73 m³ or higher.

Of the 394 patients randomized to semaglutide, 83.3% completed the study treatment and 15.7% discontinued prematurely, most often because of adverse events (9.7%). Of the remaining 394 patients randomized to canagliflozin therapy, 87.1% completed treatment and 12.9% discontinued prematurely, again mostly for adverse events (5.1%).

Overall the rate of any adverse events (76.0% vs. 71.8%) or serious adverse events (4.6% vs. 5.3%) were similar between the semaglutide and canagliflozin groups. As expected, more gastrointestinal side effects were seen in patients treated with semaglutide than in those treated with canagliflozin (46.9% vs. 27.9%), and there were more infections in the canagliflozin group (29.1% vs. 34.5%). Hypoglycemic episodes were “very rare in this population,” Dr. Lingvay reported. Rates of severe or confirmed hypoglycemia were 1.5% and 1.3% for the respective arms.

Other findings of note were improved fasting blood lipids – with greater changes in total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides seen with semaglutide than canagliflozin. Systolic blood pressure dropped in both groups, with a greater change in the canagliflozin than semaglutide group (–5.5 mm Hg vs. –3.5 mm Hg; P = .0452).

In a substudy of SUSTAIN 8 (n = 178), which was reported separately at the meeting, both semaglutide and canagliflozin reduced total fat mass as assessed with whole-body, dual-energy x-ray absorptiometry scanning. The changes in total fat mass from baseline to week 52 were a respective –3.4 kg and –2.6, or 1.4% and 1.2%. Total lean mass changed by a respective –2.3 kg and –1.5 kg (1.2% and 1.1%), and visceral fat mass by –0.2 kg and –0.1 kg (–0.9% and 0.4%). There was no statistical significance between the groups. A post hoc analysis did show, however, that a greater drop in waist circumference might be achieved with semaglutide than with canagliflozin (–4.0 vs. –2.9 cm [–3.9% vs. –2.5%], P = .02).

“Importantly, neither treatment was associated with deleterious body composition changes, such as gains in fat mass or reductions in the total lean mass,” said Rory McCrimmon, MBChB, professor of experimental diabetes and metabolism at the University of Dundee, Scotland, when presenting the substudy findings.

“These findings are consistent with results from other body composition studies with GLP-1 RAs and SGLT2 [inhibitors],”Dr. McCrimmon said, adding that “the positive effects on total fat loss and visceral fat reduction highlight the role of semaglutide and canagliflozin as relevant treatment options for patients with type 2 diabetes.”

Novo Nordisk funded the study. Dr. Lingvay has received consulting fees from Novo Nordisk; research grants from her institution; and grants, personal fees, or both, from other companies not related to the study. Dr. McCrimmon has received personal fees from Novo Nordisk and two other companies.
 

SOURCES: Lingvay I et al. Lancet Diabetes Endocrinol. 2019 Sep 17. doi: 10.1016/S2213-8587(19)30311-0; McCrimmon RJ et al. EASD 2019, Abstract 54.

HIV positivity does not preclude chimeric antigen receptor (CAR) T-cell therapy for patients with aggressive lymphoma, a report of two cases suggests. Both of the HIV-positive patients, one of whom had long-term psychiatric comorbidity, achieved durable remission on axicabtagene ciloleucel (Yescarta) without undue toxicity.

Cynthia Goldsmith, CDC

“To our knowledge, these are the first reported cases of CAR T-cell therapy administered to HIV-infected patients with lymphoma,” Jeremy S. Abramson, MD, of Massachusetts General Hospital, Boston and his colleagues wrote in Cancer. “Patients with HIV and AIDS, as well as those with preexisting mental illness, should not be considered disqualified from CAR T-cell therapy and deserve ongoing studies to optimize efficacy and safety in this population.”

The Food and Drug Administration has approved two CAR T-cell products that target the B-cell antigen CD19 for the treatment of refractory lymphoma. But their efficacy and safety in HIV-positive patients are unknown because this group has been excluded from pivotal clinical trials.

Dr. Abramson and coauthors detail the two cases of successful anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel in patients with HIV-associated, refractory, high-grade B-cell lymphoma.

The first patient was an HIV-positive man with diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype who was intermittently adherent to antiretroviral therapy. His comorbidities included posttraumatic stress disorder and schizoaffective disorder.

Previous treatments for DLBCL included dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), and rituximab, ifosfamide, carboplatin, and etoposide (RICE). A recurrence precluded high-dose chemotherapy with autologous stem cell support.

With close multidisciplinary management, including psychiatric consultation, the patient became a candidate for CAR T-cell therapy and received axicabtagene ciloleucel. He experienced grade 2 cytokine release syndrome and grade 3 neurologic toxicity, both of which resolved with treatment. Imaging showed complete remission at approximately 3 months that was sustained at 1 year. Additionally, he had an undetectable HIV viral load and was psychiatrically stable.

The second patient was a man with AIDS-associated, non–germinal center B-cell, Epstein-Barr virus–positive DLBCL who was adherent to antiretroviral therapy. His lymphoma had recurred rapidly after initially responding to dose-adjusted EPOCH-R and then was refractory to combination rituximab and lenalidomide. He previously had hepatitis B virus, cytomegalovirus, and Mycobacterium avium complex infections.

Because of prolonged cytopenias and infectious complications after the previous lymphoma treatments, the patient was considered a poor candidate for high-dose chemotherapy. He underwent CAR T-cell therapy with axicabtagene ciloleucel and had a complete remission on day 28. Additionally, his HIV infection remained well controlled.

“Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, high-grade B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission,” the researchers wrote. “These cases have further demonstrated the proactive, multidisciplinary care required to navigate a patient with high-risk lymphoma through CAR T-cell therapy with attention to significant medical and psychiatric comorbidities.”

Dr. Abramson reported that he has acted as a paid member of the scientific advisory board and as a paid consultant for Kite Pharma, which markets Yescarta, and several other companies.

SOURCE: Abramson JS et al. Cancer. 2019 Sep 10. doi: 10.1002/cncr.32411.

HIV positivity does not preclude chimeric antigen receptor (CAR) T-cell therapy for patients with aggressive lymphoma, a report of two cases suggests. Both of the HIV-positive patients, one of whom had long-term psychiatric comorbidity, achieved durable remission on axicabtagene ciloleucel (Yescarta) without undue toxicity.

Cynthia Goldsmith, CDC

“To our knowledge, these are the first reported cases of CAR T-cell therapy administered to HIV-infected patients with lymphoma,” Jeremy S. Abramson, MD, of Massachusetts General Hospital, Boston and his colleagues wrote in Cancer. “Patients with HIV and AIDS, as well as those with preexisting mental illness, should not be considered disqualified from CAR T-cell therapy and deserve ongoing studies to optimize efficacy and safety in this population.”

The Food and Drug Administration has approved two CAR T-cell products that target the B-cell antigen CD19 for the treatment of refractory lymphoma. But their efficacy and safety in HIV-positive patients are unknown because this group has been excluded from pivotal clinical trials.

Dr. Abramson and coauthors detail the two cases of successful anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel in patients with HIV-associated, refractory, high-grade B-cell lymphoma.

The first patient was an HIV-positive man with diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype who was intermittently adherent to antiretroviral therapy. His comorbidities included posttraumatic stress disorder and schizoaffective disorder.

Previous treatments for DLBCL included dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), and rituximab, ifosfamide, carboplatin, and etoposide (RICE). A recurrence precluded high-dose chemotherapy with autologous stem cell support.

With close multidisciplinary management, including psychiatric consultation, the patient became a candidate for CAR T-cell therapy and received axicabtagene ciloleucel. He experienced grade 2 cytokine release syndrome and grade 3 neurologic toxicity, both of which resolved with treatment. Imaging showed complete remission at approximately 3 months that was sustained at 1 year. Additionally, he had an undetectable HIV viral load and was psychiatrically stable.

The second patient was a man with AIDS-associated, non–germinal center B-cell, Epstein-Barr virus–positive DLBCL who was adherent to antiretroviral therapy. His lymphoma had recurred rapidly after initially responding to dose-adjusted EPOCH-R and then was refractory to combination rituximab and lenalidomide. He previously had hepatitis B virus, cytomegalovirus, and Mycobacterium avium complex infections.

Because of prolonged cytopenias and infectious complications after the previous lymphoma treatments, the patient was considered a poor candidate for high-dose chemotherapy. He underwent CAR T-cell therapy with axicabtagene ciloleucel and had a complete remission on day 28. Additionally, his HIV infection remained well controlled.

“Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, high-grade B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission,” the researchers wrote. “These cases have further demonstrated the proactive, multidisciplinary care required to navigate a patient with high-risk lymphoma through CAR T-cell therapy with attention to significant medical and psychiatric comorbidities.”

Dr. Abramson reported that he has acted as a paid member of the scientific advisory board and as a paid consultant for Kite Pharma, which markets Yescarta, and several other companies.

SOURCE: Abramson JS et al. Cancer. 2019 Sep 10. doi: 10.1002/cncr.32411.

HIV positivity does not preclude chimeric antigen receptor (CAR) T-cell therapy for patients with aggressive lymphoma, a report of two cases suggests. Both of the HIV-positive patients, one of whom had long-term psychiatric comorbidity, achieved durable remission on axicabtagene ciloleucel (Yescarta) without undue toxicity.

Cynthia Goldsmith, CDC

“To our knowledge, these are the first reported cases of CAR T-cell therapy administered to HIV-infected patients with lymphoma,” Jeremy S. Abramson, MD, of Massachusetts General Hospital, Boston and his colleagues wrote in Cancer. “Patients with HIV and AIDS, as well as those with preexisting mental illness, should not be considered disqualified from CAR T-cell therapy and deserve ongoing studies to optimize efficacy and safety in this population.”

The Food and Drug Administration has approved two CAR T-cell products that target the B-cell antigen CD19 for the treatment of refractory lymphoma. But their efficacy and safety in HIV-positive patients are unknown because this group has been excluded from pivotal clinical trials.

Dr. Abramson and coauthors detail the two cases of successful anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel in patients with HIV-associated, refractory, high-grade B-cell lymphoma.

The first patient was an HIV-positive man with diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype who was intermittently adherent to antiretroviral therapy. His comorbidities included posttraumatic stress disorder and schizoaffective disorder.

Previous treatments for DLBCL included dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), and rituximab, ifosfamide, carboplatin, and etoposide (RICE). A recurrence precluded high-dose chemotherapy with autologous stem cell support.

With close multidisciplinary management, including psychiatric consultation, the patient became a candidate for CAR T-cell therapy and received axicabtagene ciloleucel. He experienced grade 2 cytokine release syndrome and grade 3 neurologic toxicity, both of which resolved with treatment. Imaging showed complete remission at approximately 3 months that was sustained at 1 year. Additionally, he had an undetectable HIV viral load and was psychiatrically stable.

The second patient was a man with AIDS-associated, non–germinal center B-cell, Epstein-Barr virus–positive DLBCL who was adherent to antiretroviral therapy. His lymphoma had recurred rapidly after initially responding to dose-adjusted EPOCH-R and then was refractory to combination rituximab and lenalidomide. He previously had hepatitis B virus, cytomegalovirus, and Mycobacterium avium complex infections.

Because of prolonged cytopenias and infectious complications after the previous lymphoma treatments, the patient was considered a poor candidate for high-dose chemotherapy. He underwent CAR T-cell therapy with axicabtagene ciloleucel and had a complete remission on day 28. Additionally, his HIV infection remained well controlled.

“Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, high-grade B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission,” the researchers wrote. “These cases have further demonstrated the proactive, multidisciplinary care required to navigate a patient with high-risk lymphoma through CAR T-cell therapy with attention to significant medical and psychiatric comorbidities.”

Dr. Abramson reported that he has acted as a paid member of the scientific advisory board and as a paid consultant for Kite Pharma, which markets Yescarta, and several other companies.

SOURCE: Abramson JS et al. Cancer. 2019 Sep 10. doi: 10.1002/cncr.32411.