The SVS Foundation has extended the application deadline for its prestigious Resident Research Award to Tuesday, Jan. 22. This award is one of the most important opportunities for surgical trainees in vascular laboratories and includes the opportunity for the recipient to showcase his or her work in a podium presentation at the 2019 Vascular Annual Meeting. In addition, the recipient receives a $5,000 award. This year’s VAM is June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., outside of Washington, D.C. Find award details and guidelines here.

The SVS Foundation has extended the application deadline for its prestigious Resident Research Award to Tuesday, Jan. 22. This award is one of the most important opportunities for surgical trainees in vascular laboratories and includes the opportunity for the recipient to showcase his or her work in a podium presentation at the 2019 Vascular Annual Meeting. In addition, the recipient receives a $5,000 award. This year’s VAM is June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., outside of Washington, D.C. Find award details and guidelines here.

The SVS Foundation has extended the application deadline for its prestigious Resident Research Award to Tuesday, Jan. 22. This award is one of the most important opportunities for surgical trainees in vascular laboratories and includes the opportunity for the recipient to showcase his or her work in a podium presentation at the 2019 Vascular Annual Meeting. In addition, the recipient receives a $5,000 award. This year’s VAM is June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., outside of Washington, D.C. Find award details and guidelines here.

While most outcomes are similar between robotic surgery and laparoscopic surgery for sleeve gastrectomy, the robotic approach carried a greater risk of organ space infection, according to the findings from a large clinical trial of more than 100,000 patients.

The study’s authors analyzed 107,726 sleeve gastrectomy operations in the Metabolic and Bariatric Surgery Association and Quality Improvement Program data registry (MBSAQIP), 7,385 of which were robotic sleeve gastrectomy (RSG). Peter William Lundberg, MD, and his coauthors of St. Luke’s University Health Network, Bethlehem, Pa., evaluated the safety of RSG vs. laparoscopic sleeve gastrectomy (LSG). The study was the first and largest comparing the two approaches to sleeve gastrectomy, the researchers noted.

“According to the MBSAQIP database, the robotic approach demonstrates a significantly higher rate of organ space infection while trending toward a lower rate of bleeding and 30-day reoperation and intervention,” Dr. Lundberg and his coauthors said.

Overall mortality was 0.07% in both groups (P = .49). The overall rates of significant adverse events were similar in both groups – 1.3% for LSG and 1.1% for RSG (P = .14) – as were bleeding rates – 0.5% and 0.4% (P = .003), respectively. The investigators characterized the slightly lower rates for RSG as “insignificant.”

RSG, however, had three times the rate of organ space infection than did the laparoscopic approach, 0.3% vs. 0.1% (P = .79). “Considering the enthusiasm with which robotics has been adopted by some bariatric surgeons, this is a sobering finding,” Dr. Lundberg noted.

The study determined that the use of staple-line reinforcement (SLR) alone significantly reduced the rate of bleeding regardless of approach by 31% on average (P = .0005). “This risk reduction was enhanced when SLR was combined with oversewing of the staple line,” Dr. Lundberg and his colleagues noted – an average reduction of 42% (P = .0009).

RSG took longer on average, 89 minutes vs. 63 minutes (P less than .0001), and the average length of stay was almost identical, 1.7 for RSG vs. 1.6 days for LSG. Reoperation rates within 30 days were also similar: 0.7% for RSG vs. 0.8% for LSG (P = .003).

“As surgeons continue to adopt and develop new technology, ongoing monitoring and reporting of safety and outcomes data are advised to maintain the high standards for outcomes in bariatric surgery,” Dr. Lundberg and his coauthors said.

The study researchers had no financial conflicts.

SOURCE: Lundberg PW et al. Surg Obes Relat Dis. 2018 Oct 25. doi:10.1016/j.soard.2018.10.015.
 

While most outcomes are similar between robotic surgery and laparoscopic surgery for sleeve gastrectomy, the robotic approach carried a greater risk of organ space infection, according to the findings from a large clinical trial of more than 100,000 patients.

The study’s authors analyzed 107,726 sleeve gastrectomy operations in the Metabolic and Bariatric Surgery Association and Quality Improvement Program data registry (MBSAQIP), 7,385 of which were robotic sleeve gastrectomy (RSG). Peter William Lundberg, MD, and his coauthors of St. Luke’s University Health Network, Bethlehem, Pa., evaluated the safety of RSG vs. laparoscopic sleeve gastrectomy (LSG). The study was the first and largest comparing the two approaches to sleeve gastrectomy, the researchers noted.

“According to the MBSAQIP database, the robotic approach demonstrates a significantly higher rate of organ space infection while trending toward a lower rate of bleeding and 30-day reoperation and intervention,” Dr. Lundberg and his coauthors said.

Overall mortality was 0.07% in both groups (P = .49). The overall rates of significant adverse events were similar in both groups – 1.3% for LSG and 1.1% for RSG (P = .14) – as were bleeding rates – 0.5% and 0.4% (P = .003), respectively. The investigators characterized the slightly lower rates for RSG as “insignificant.”

RSG, however, had three times the rate of organ space infection than did the laparoscopic approach, 0.3% vs. 0.1% (P = .79). “Considering the enthusiasm with which robotics has been adopted by some bariatric surgeons, this is a sobering finding,” Dr. Lundberg noted.

The study determined that the use of staple-line reinforcement (SLR) alone significantly reduced the rate of bleeding regardless of approach by 31% on average (P = .0005). “This risk reduction was enhanced when SLR was combined with oversewing of the staple line,” Dr. Lundberg and his colleagues noted – an average reduction of 42% (P = .0009).

RSG took longer on average, 89 minutes vs. 63 minutes (P less than .0001), and the average length of stay was almost identical, 1.7 for RSG vs. 1.6 days for LSG. Reoperation rates within 30 days were also similar: 0.7% for RSG vs. 0.8% for LSG (P = .003).

“As surgeons continue to adopt and develop new technology, ongoing monitoring and reporting of safety and outcomes data are advised to maintain the high standards for outcomes in bariatric surgery,” Dr. Lundberg and his coauthors said.

The study researchers had no financial conflicts.

SOURCE: Lundberg PW et al. Surg Obes Relat Dis. 2018 Oct 25. doi:10.1016/j.soard.2018.10.015.
 

While most outcomes are similar between robotic surgery and laparoscopic surgery for sleeve gastrectomy, the robotic approach carried a greater risk of organ space infection, according to the findings from a large clinical trial of more than 100,000 patients.

The study’s authors analyzed 107,726 sleeve gastrectomy operations in the Metabolic and Bariatric Surgery Association and Quality Improvement Program data registry (MBSAQIP), 7,385 of which were robotic sleeve gastrectomy (RSG). Peter William Lundberg, MD, and his coauthors of St. Luke’s University Health Network, Bethlehem, Pa., evaluated the safety of RSG vs. laparoscopic sleeve gastrectomy (LSG). The study was the first and largest comparing the two approaches to sleeve gastrectomy, the researchers noted.

“According to the MBSAQIP database, the robotic approach demonstrates a significantly higher rate of organ space infection while trending toward a lower rate of bleeding and 30-day reoperation and intervention,” Dr. Lundberg and his coauthors said.

Overall mortality was 0.07% in both groups (P = .49). The overall rates of significant adverse events were similar in both groups – 1.3% for LSG and 1.1% for RSG (P = .14) – as were bleeding rates – 0.5% and 0.4% (P = .003), respectively. The investigators characterized the slightly lower rates for RSG as “insignificant.”

RSG, however, had three times the rate of organ space infection than did the laparoscopic approach, 0.3% vs. 0.1% (P = .79). “Considering the enthusiasm with which robotics has been adopted by some bariatric surgeons, this is a sobering finding,” Dr. Lundberg noted.

The study determined that the use of staple-line reinforcement (SLR) alone significantly reduced the rate of bleeding regardless of approach by 31% on average (P = .0005). “This risk reduction was enhanced when SLR was combined with oversewing of the staple line,” Dr. Lundberg and his colleagues noted – an average reduction of 42% (P = .0009).

RSG took longer on average, 89 minutes vs. 63 minutes (P less than .0001), and the average length of stay was almost identical, 1.7 for RSG vs. 1.6 days for LSG. Reoperation rates within 30 days were also similar: 0.7% for RSG vs. 0.8% for LSG (P = .003).

“As surgeons continue to adopt and develop new technology, ongoing monitoring and reporting of safety and outcomes data are advised to maintain the high standards for outcomes in bariatric surgery,” Dr. Lundberg and his coauthors said.

The study researchers had no financial conflicts.

SOURCE: Lundberg PW et al. Surg Obes Relat Dis. 2018 Oct 25. doi:10.1016/j.soard.2018.10.015.
 

In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.

The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.

The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.

Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.

Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.

At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.

However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).

Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.

The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.

“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.

The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.

SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.

In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.

The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.

The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.

Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.

Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.

At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.

However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).

Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.

The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.

“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.

The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.

SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.

In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.

The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.

The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.

Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.

Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.

At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.

However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).

Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.

The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.

“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.

The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.

SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.

PARIS – The interleukin-17 receptor inhibitor brodalumab achieved complete clearance of moderate-to-severe psoriasis far faster and more frequently than the interleukin-12/23 inhibitor ustekinumab.

Bruce Jancin/MDedge News

That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.

“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.

Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.

“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”

His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.

It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.

This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.

Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.

The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.

Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.

[email protected]

SOURCE: Reich K. EADV Congress, Abstract #FC03.06.

PARIS – The interleukin-17 receptor inhibitor brodalumab achieved complete clearance of moderate-to-severe psoriasis far faster and more frequently than the interleukin-12/23 inhibitor ustekinumab.

Bruce Jancin/MDedge News

That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.

“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.

Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.

“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”

His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.

It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.

This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.

Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.

The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.

Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.

[email protected]

SOURCE: Reich K. EADV Congress, Abstract #FC03.06.

PARIS – The interleukin-17 receptor inhibitor brodalumab achieved complete clearance of moderate-to-severe psoriasis far faster and more frequently than the interleukin-12/23 inhibitor ustekinumab.

Bruce Jancin/MDedge News

That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.

“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.

Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.

“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”

His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.

It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.

This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.

Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.

The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.

Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.

[email protected]

SOURCE: Reich K. EADV Congress, Abstract #FC03.06.

The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.

Andrew D. Bowser/MDedge News

The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.

While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, the OSA diagnosis remained a significant risk factor for arrhythmias in this group of patients, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.

“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.

The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.

With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.

Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.

The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.

Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.

While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.

Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.

This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.

Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.

“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.

The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.

SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.

The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.

Andrew D. Bowser/MDedge News

The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.

While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, the OSA diagnosis remained a significant risk factor for arrhythmias in this group of patients, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.

“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.

The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.

With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.

Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.

The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.

Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.

While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.

Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.

This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.

Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.

“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.

The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.

SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.

The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.

Andrew D. Bowser/MDedge News

The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.

While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, the OSA diagnosis remained a significant risk factor for arrhythmias in this group of patients, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.

“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.

The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.

With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.

Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.

The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.

Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.

While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.

Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.

This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.

Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.

“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.

The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.

SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.

LOS ANGELES – Mounting evidence suggests that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors helps prevent heart failure.

They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.

“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”

Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.

“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.

“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.

The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.

“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”

Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”

The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”

Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.

“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”

SGLT-2 inhibitors convey a different story.

In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.

However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).

“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”

A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).

Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.

“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.

“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”

A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.

Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”

Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).

Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.

[email protected]

LOS ANGELES – Mounting evidence suggests that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors helps prevent heart failure.

They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.

“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”

Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.

“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.

“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.

The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.

“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”

Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”

The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”

Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.

“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”

SGLT-2 inhibitors convey a different story.

In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.

However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).

“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”

A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).

Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.

“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.

“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”

A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.

Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”

Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).

Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.

[email protected]

LOS ANGELES – Mounting evidence suggests that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors helps prevent heart failure.

They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.

“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”

Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.

“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.

“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.

The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.

“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”

Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”

The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”

Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.

“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”

SGLT-2 inhibitors convey a different story.

In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.

However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).

“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”

A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).

Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.

“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.

“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”

A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.

Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”

Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).

Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.

[email protected]

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.

Kenishirotie/Thinkstock

According to new research, the costs of oral and injectable brand-name drugs increased annually during 2008-2016 by 9.2% and 15.1%, respectively, largely driven by existing drug prices.

For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.

Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.

“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.

“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.

“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.

Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.

The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.

“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”

The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.

The authors provided no disclosures.
 

[email protected]

SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.

Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.

Kenishirotie/Thinkstock

According to new research, the costs of oral and injectable brand-name drugs increased annually during 2008-2016 by 9.2% and 15.1%, respectively, largely driven by existing drug prices.

For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.

Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.

“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.

“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.

“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.

Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.

The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.

“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”

The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.

The authors provided no disclosures.
 

[email protected]

SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.

Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.

Kenishirotie/Thinkstock

According to new research, the costs of oral and injectable brand-name drugs increased annually during 2008-2016 by 9.2% and 15.1%, respectively, largely driven by existing drug prices.

For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.

Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.

“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.

“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.

“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.

Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.

The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.

“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”

The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.

The authors provided no disclosures.
 

[email protected]

SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

In this special edition of the MDedge Daily News, Nick Andrews and Terry Rudd report the latest news from the 2018 San Antonio Breast Cancer Symposium. Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

In this special edition of the MDedge Daily News, Nick Andrews and Terry Rudd report the latest news from the 2018 San Antonio Breast Cancer Symposium. Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

In this special edition of the MDedge Daily News, Nick Andrews and Terry Rudd report the latest news from the 2018 San Antonio Breast Cancer Symposium. Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify