CHICAGO – Patients who have one kidney do as well after fenestrated-branched endovascular aneurysm repair (F-BEVAR) of pararenal or thoracoabdominal aortic aneurysm as patients with both kidneys, according to a study of almost 300 patients presented at the annual meeting of the Midwestern Vascular Surgery Society.

“Despite the worse baseline renal function associated with single functioning kidney patients, F-BEVAR is safe and effective with nearly identical outcomes in patients with a SFK [single functioning kidney] as compared to patients with two functioning kidneys,” said Keouna Pather of Mayo Clinic, Rochester, Minn.

The study evaluated 287 F-BEVAR patients enrolled in a physician-sponsored investigation device exemption study from November 2013 to October 2018. Thirty of those patients had one kidney, the remaining 257 were the control group. Ms. Pather noted that characteristics were similar between both patient groups with the exception that SFK patients were younger (age 70 vs. 74 years; P = .009) and had larger renal artery diameter (6 vs. 5.7 mm; P = .05). “Patients with a SFK had enlargement of their renal artery in a compensatory fashion,” she said.

Survival at 2 years was 92% for SFK patients and 84% for controls.

“The SFK patients did start at a worse baseline of CKD [chronic kidney disease] stages as compared to controls,” she noted. In the SFK group, 63% (n = 19) had Stage III CKD versus 40% (n = 104) of controls (P = .02). Likewise, rates of Stage IV CKD were 10% (n = 3) and 2% (n = 4), respectively (P = .03).

In terms of outcomes, two patients in the control group died within 30 days but none in the SFK group did, Ms. Pather said. Also, a higher percentage of SFK patients had estimated blood loss greater than 1 L, compared with controls (20% vs. 7%; P = .02). All other outcomes, including rates of acute kidney injury (20% vs. 12%; P = .26), were not statistically different, she said.

“Between the groups, there was no significant difference in CKD progression that needed stenting,” she added, with 27% (n = 8) and 26% (n = 67) of the SFK and controls progressing to CKD Stages III to V.

The study also identified predictors of acute kidney injury in SFK patients: total fluoroscopy time (hours), which raised the risk by 78.5%, and estimated blood loss greater than 1 L, which increased risk by 109%.

Predictors of renal function deterioration in SFK patients were renal artery occlusion or reintervention for branch stenosis or kink, which raised the risk threefold; a Crawford extent II, which more than doubled the risk; and acute kidney injury, which raised chances almost fivefold. “Development of postoperative AKI [acute kidney injury] is the most important predictor for renal function deterioration,” Pather said.

When freedom from renal function deterioration at 2 years was compared between the two groups, again the results were similar because of the small sample size of the SFK group: 100% for the SFK group and 84% for controls.

Ms. Pather had no financial relationships to disclose.

CHICAGO – Patients who have one kidney do as well after fenestrated-branched endovascular aneurysm repair (F-BEVAR) of pararenal or thoracoabdominal aortic aneurysm as patients with both kidneys, according to a study of almost 300 patients presented at the annual meeting of the Midwestern Vascular Surgery Society.

“Despite the worse baseline renal function associated with single functioning kidney patients, F-BEVAR is safe and effective with nearly identical outcomes in patients with a SFK [single functioning kidney] as compared to patients with two functioning kidneys,” said Keouna Pather of Mayo Clinic, Rochester, Minn.

The study evaluated 287 F-BEVAR patients enrolled in a physician-sponsored investigation device exemption study from November 2013 to October 2018. Thirty of those patients had one kidney, the remaining 257 were the control group. Ms. Pather noted that characteristics were similar between both patient groups with the exception that SFK patients were younger (age 70 vs. 74 years; P = .009) and had larger renal artery diameter (6 vs. 5.7 mm; P = .05). “Patients with a SFK had enlargement of their renal artery in a compensatory fashion,” she said.

Survival at 2 years was 92% for SFK patients and 84% for controls.

“The SFK patients did start at a worse baseline of CKD [chronic kidney disease] stages as compared to controls,” she noted. In the SFK group, 63% (n = 19) had Stage III CKD versus 40% (n = 104) of controls (P = .02). Likewise, rates of Stage IV CKD were 10% (n = 3) and 2% (n = 4), respectively (P = .03).

In terms of outcomes, two patients in the control group died within 30 days but none in the SFK group did, Ms. Pather said. Also, a higher percentage of SFK patients had estimated blood loss greater than 1 L, compared with controls (20% vs. 7%; P = .02). All other outcomes, including rates of acute kidney injury (20% vs. 12%; P = .26), were not statistically different, she said.

“Between the groups, there was no significant difference in CKD progression that needed stenting,” she added, with 27% (n = 8) and 26% (n = 67) of the SFK and controls progressing to CKD Stages III to V.

The study also identified predictors of acute kidney injury in SFK patients: total fluoroscopy time (hours), which raised the risk by 78.5%, and estimated blood loss greater than 1 L, which increased risk by 109%.

Predictors of renal function deterioration in SFK patients were renal artery occlusion or reintervention for branch stenosis or kink, which raised the risk threefold; a Crawford extent II, which more than doubled the risk; and acute kidney injury, which raised chances almost fivefold. “Development of postoperative AKI [acute kidney injury] is the most important predictor for renal function deterioration,” Pather said.

When freedom from renal function deterioration at 2 years was compared between the two groups, again the results were similar because of the small sample size of the SFK group: 100% for the SFK group and 84% for controls.

Ms. Pather had no financial relationships to disclose.

CHICAGO – Patients who have one kidney do as well after fenestrated-branched endovascular aneurysm repair (F-BEVAR) of pararenal or thoracoabdominal aortic aneurysm as patients with both kidneys, according to a study of almost 300 patients presented at the annual meeting of the Midwestern Vascular Surgery Society.

“Despite the worse baseline renal function associated with single functioning kidney patients, F-BEVAR is safe and effective with nearly identical outcomes in patients with a SFK [single functioning kidney] as compared to patients with two functioning kidneys,” said Keouna Pather of Mayo Clinic, Rochester, Minn.

The study evaluated 287 F-BEVAR patients enrolled in a physician-sponsored investigation device exemption study from November 2013 to October 2018. Thirty of those patients had one kidney, the remaining 257 were the control group. Ms. Pather noted that characteristics were similar between both patient groups with the exception that SFK patients were younger (age 70 vs. 74 years; P = .009) and had larger renal artery diameter (6 vs. 5.7 mm; P = .05). “Patients with a SFK had enlargement of their renal artery in a compensatory fashion,” she said.

Survival at 2 years was 92% for SFK patients and 84% for controls.

“The SFK patients did start at a worse baseline of CKD [chronic kidney disease] stages as compared to controls,” she noted. In the SFK group, 63% (n = 19) had Stage III CKD versus 40% (n = 104) of controls (P = .02). Likewise, rates of Stage IV CKD were 10% (n = 3) and 2% (n = 4), respectively (P = .03).

In terms of outcomes, two patients in the control group died within 30 days but none in the SFK group did, Ms. Pather said. Also, a higher percentage of SFK patients had estimated blood loss greater than 1 L, compared with controls (20% vs. 7%; P = .02). All other outcomes, including rates of acute kidney injury (20% vs. 12%; P = .26), were not statistically different, she said.

“Between the groups, there was no significant difference in CKD progression that needed stenting,” she added, with 27% (n = 8) and 26% (n = 67) of the SFK and controls progressing to CKD Stages III to V.

The study also identified predictors of acute kidney injury in SFK patients: total fluoroscopy time (hours), which raised the risk by 78.5%, and estimated blood loss greater than 1 L, which increased risk by 109%.

Predictors of renal function deterioration in SFK patients were renal artery occlusion or reintervention for branch stenosis or kink, which raised the risk threefold; a Crawford extent II, which more than doubled the risk; and acute kidney injury, which raised chances almost fivefold. “Development of postoperative AKI [acute kidney injury] is the most important predictor for renal function deterioration,” Pather said.

When freedom from renal function deterioration at 2 years was compared between the two groups, again the results were similar because of the small sample size of the SFK group: 100% for the SFK group and 84% for controls.

Ms. Pather had no financial relationships to disclose.

New results for secukinumab (Cosentyx) in the PREVENT trial continue its promising trend for treatment of the full spectrum of axial spondyloarthritis (axSpA), according to a release from Novartis. The PREVENT trial is assessing this therapy in nonradiographic axSpA (nr-axSpA); it’s already approved in ankylosing spondylitis.

Results of 16-week data were presented in mid-September, and the new results represent 52-week data. Full details and data will be revealed at an upcoming scientific congress.

The PREVENT trial is an ongoing, 2-year trial with a 2-year extension phase; it enrolled 550 men and women with nr-axSpA and assessed their response to secukinumab with an induction phase, to it without induction, or to placebo. The trial met its primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS40) criteria at 16 and 52 weeks, which indicates meaningful and sustained improvement. ASAS40 is defined as an improvement of at least 40% and both 10 out of 100 points in three of four domains (patient global assessment, pain, function, and inflammation) and no worsening in the remaining one. The safety profile in this trial was consistent with those seen in previous trials.

Overall, the most common adverse reactions seen with this interleukin-17A antagonist are nasopharyngitis, diarrhea, and upper respiratory tract infections. Patients should be evaluated for tuberculosis before initiating treatment. Serious infections have been observed, so be mindful of patients with chronic infections and discontinue secukinumab in patients who develop infections. Caution should be exercised when prescribing to patients with inflammatory bowel disease. Full prescribing information can be found on the Novartis website.

cpalmer@mdedge.com

New results for secukinumab (Cosentyx) in the PREVENT trial continue its promising trend for treatment of the full spectrum of axial spondyloarthritis (axSpA), according to a release from Novartis. The PREVENT trial is assessing this therapy in nonradiographic axSpA (nr-axSpA); it’s already approved in ankylosing spondylitis.

Results of 16-week data were presented in mid-September, and the new results represent 52-week data. Full details and data will be revealed at an upcoming scientific congress.

The PREVENT trial is an ongoing, 2-year trial with a 2-year extension phase; it enrolled 550 men and women with nr-axSpA and assessed their response to secukinumab with an induction phase, to it without induction, or to placebo. The trial met its primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS40) criteria at 16 and 52 weeks, which indicates meaningful and sustained improvement. ASAS40 is defined as an improvement of at least 40% and both 10 out of 100 points in three of four domains (patient global assessment, pain, function, and inflammation) and no worsening in the remaining one. The safety profile in this trial was consistent with those seen in previous trials.

Overall, the most common adverse reactions seen with this interleukin-17A antagonist are nasopharyngitis, diarrhea, and upper respiratory tract infections. Patients should be evaluated for tuberculosis before initiating treatment. Serious infections have been observed, so be mindful of patients with chronic infections and discontinue secukinumab in patients who develop infections. Caution should be exercised when prescribing to patients with inflammatory bowel disease. Full prescribing information can be found on the Novartis website.

cpalmer@mdedge.com

New results for secukinumab (Cosentyx) in the PREVENT trial continue its promising trend for treatment of the full spectrum of axial spondyloarthritis (axSpA), according to a release from Novartis. The PREVENT trial is assessing this therapy in nonradiographic axSpA (nr-axSpA); it’s already approved in ankylosing spondylitis.

Results of 16-week data were presented in mid-September, and the new results represent 52-week data. Full details and data will be revealed at an upcoming scientific congress.

The PREVENT trial is an ongoing, 2-year trial with a 2-year extension phase; it enrolled 550 men and women with nr-axSpA and assessed their response to secukinumab with an induction phase, to it without induction, or to placebo. The trial met its primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS40) criteria at 16 and 52 weeks, which indicates meaningful and sustained improvement. ASAS40 is defined as an improvement of at least 40% and both 10 out of 100 points in three of four domains (patient global assessment, pain, function, and inflammation) and no worsening in the remaining one. The safety profile in this trial was consistent with those seen in previous trials.

Overall, the most common adverse reactions seen with this interleukin-17A antagonist are nasopharyngitis, diarrhea, and upper respiratory tract infections. Patients should be evaluated for tuberculosis before initiating treatment. Serious infections have been observed, so be mindful of patients with chronic infections and discontinue secukinumab in patients who develop infections. Caution should be exercised when prescribing to patients with inflammatory bowel disease. Full prescribing information can be found on the Novartis website.

cpalmer@mdedge.com

New York State has reported the end of all active measles cases related to the initial outbreak in 2018, but the state is now responding to new, unrelated cases in four counties, according to the Centers for Disease Control and Prevention.

The new cases – two in Nassau County and one each in Monroe, Putnam, and Rockland counties – are “related to measles exposures from international travel but not affiliated with the 2018 outbreak,” the New York State Department of Health said in a written statement. Officials in Rockland County had declared its 2018 measles outbreak, which involved 312 cases in 2018 and 2019, over on Sept. 25.

Nationally, there have been 1,250 cases of measles reported in 31 states during 2019, the CDC reported on Oct. 7. Of those cases, 1,163 (93%) were associated with 22 outbreaks, with the two largest occurring in New York City and Rockland County. “These two almost year-long outbreaks placed the United States at risk for losing measles elimination status,” the CDC said in a separate report, but “robust responses … ended transmission before the 1-year mark.”

rfranki@mdedge.com

New York State has reported the end of all active measles cases related to the initial outbreak in 2018, but the state is now responding to new, unrelated cases in four counties, according to the Centers for Disease Control and Prevention.

The new cases – two in Nassau County and one each in Monroe, Putnam, and Rockland counties – are “related to measles exposures from international travel but not affiliated with the 2018 outbreak,” the New York State Department of Health said in a written statement. Officials in Rockland County had declared its 2018 measles outbreak, which involved 312 cases in 2018 and 2019, over on Sept. 25.

Nationally, there have been 1,250 cases of measles reported in 31 states during 2019, the CDC reported on Oct. 7. Of those cases, 1,163 (93%) were associated with 22 outbreaks, with the two largest occurring in New York City and Rockland County. “These two almost year-long outbreaks placed the United States at risk for losing measles elimination status,” the CDC said in a separate report, but “robust responses … ended transmission before the 1-year mark.”

rfranki@mdedge.com

New York State has reported the end of all active measles cases related to the initial outbreak in 2018, but the state is now responding to new, unrelated cases in four counties, according to the Centers for Disease Control and Prevention.

The new cases – two in Nassau County and one each in Monroe, Putnam, and Rockland counties – are “related to measles exposures from international travel but not affiliated with the 2018 outbreak,” the New York State Department of Health said in a written statement. Officials in Rockland County had declared its 2018 measles outbreak, which involved 312 cases in 2018 and 2019, over on Sept. 25.

Nationally, there have been 1,250 cases of measles reported in 31 states during 2019, the CDC reported on Oct. 7. Of those cases, 1,163 (93%) were associated with 22 outbreaks, with the two largest occurring in New York City and Rockland County. “These two almost year-long outbreaks placed the United States at risk for losing measles elimination status,” the CDC said in a separate report, but “robust responses … ended transmission before the 1-year mark.”

rfranki@mdedge.com

Three researchers have won the 2019 Nobel Prize in Physiology or Medicine “for their discoveries of how cells sense and adapt to oxygen availability.”

William G. Kaelin Jr., MD; Sir Peter J. Ratcliffe, MB ChB, MD; and Gregg L. Semenza, MD, PhD, described the molecular machinery that regulates gene activity in response to oxygen levels.


Their work “established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function” and “paved the way for promising new strategies to fight anemia, cancer, and many other diseases,” according to a statement by The Nobel Assembly at Karolinska Institutet.

Dr. Semenza, of Johns Hopkins Medicine in Baltimore, studied how the erythropoietin (EPO) gene is regulated by oxygen levels. Via experiments in mice, he identified DNA segments next to the EPO gene that mediate the response to hypoxia.

Dr. Ratcliffe, of the University of Oxford (England) and the Francis Crick Institute in London, also studied oxygen-dependent regulation of the EPO gene. Both his and Dr. Semenza’s groups found the oxygen-sensing mechanism was present in nearly all tissues.

Dr. Kaelin, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, was researching von Hippel-Lindau’s (VHL) syndrome, an inherited disorder in which mutations can lead to tumors in multiple organs. He found the VHL gene encodes a protein that prevents cancer onset, and cancer cells without a functional VHL gene express high levels of hypoxia-regulated genes.

Research by other groups showed that VHL is part of a complex that labels proteins with ubiquitin, tagging them for degradation. Dr. Ratcliffe and his group found that VHL is required for the degradation of HIF-1a at normal oxygen levels.

Dr. Kaelin’s and Dr. Ratcliffe’s groups also showed that, under normal oxygen conditions, hydroxyl groups are added at two locations in HIF-1a. This modification – prolyl hydroxylation – allows VHL to bind to HIF-1a. So the researchers found that normal oxygen levels control HIF-1a degradation with the help of prolyl hydroxylases.

Additional research by Dr. Ratcliffe’s group and others revealed the specific prolyl hydroxylases involved in HIF-1a degradation. The researchers also found that HIF-1a’s gene-activating function was regulated by oxygen-dependent hydroxylation.

This work has improved the understanding of how different oxygen levels regulate physiological processes. In particular, oxygen sensing is essential for erythropoiesis, so these findings have implications for the treatment of anemia.

“There are several drugs that are now in clinical trials that serve to increase HIF activity and, as a result, will increase the production of erythropoietin and stimulate red blood cell production,” Dr. Semenza said in an interview after the announcement of his Nobel win. “These are all small molecules that can be given by mouth, and that may be a great convenience for patients who, at the present time, may require injections of recombinant human erythropoietin.”

jensmith@mdedge.com

Three researchers have won the 2019 Nobel Prize in Physiology or Medicine “for their discoveries of how cells sense and adapt to oxygen availability.”

William G. Kaelin Jr., MD; Sir Peter J. Ratcliffe, MB ChB, MD; and Gregg L. Semenza, MD, PhD, described the molecular machinery that regulates gene activity in response to oxygen levels.


Their work “established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function” and “paved the way for promising new strategies to fight anemia, cancer, and many other diseases,” according to a statement by The Nobel Assembly at Karolinska Institutet.

Dr. Semenza, of Johns Hopkins Medicine in Baltimore, studied how the erythropoietin (EPO) gene is regulated by oxygen levels. Via experiments in mice, he identified DNA segments next to the EPO gene that mediate the response to hypoxia.

Dr. Ratcliffe, of the University of Oxford (England) and the Francis Crick Institute in London, also studied oxygen-dependent regulation of the EPO gene. Both his and Dr. Semenza’s groups found the oxygen-sensing mechanism was present in nearly all tissues.

Dr. Kaelin, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, was researching von Hippel-Lindau’s (VHL) syndrome, an inherited disorder in which mutations can lead to tumors in multiple organs. He found the VHL gene encodes a protein that prevents cancer onset, and cancer cells without a functional VHL gene express high levels of hypoxia-regulated genes.

Research by other groups showed that VHL is part of a complex that labels proteins with ubiquitin, tagging them for degradation. Dr. Ratcliffe and his group found that VHL is required for the degradation of HIF-1a at normal oxygen levels.

Dr. Kaelin’s and Dr. Ratcliffe’s groups also showed that, under normal oxygen conditions, hydroxyl groups are added at two locations in HIF-1a. This modification – prolyl hydroxylation – allows VHL to bind to HIF-1a. So the researchers found that normal oxygen levels control HIF-1a degradation with the help of prolyl hydroxylases.

Additional research by Dr. Ratcliffe’s group and others revealed the specific prolyl hydroxylases involved in HIF-1a degradation. The researchers also found that HIF-1a’s gene-activating function was regulated by oxygen-dependent hydroxylation.

This work has improved the understanding of how different oxygen levels regulate physiological processes. In particular, oxygen sensing is essential for erythropoiesis, so these findings have implications for the treatment of anemia.

“There are several drugs that are now in clinical trials that serve to increase HIF activity and, as a result, will increase the production of erythropoietin and stimulate red blood cell production,” Dr. Semenza said in an interview after the announcement of his Nobel win. “These are all small molecules that can be given by mouth, and that may be a great convenience for patients who, at the present time, may require injections of recombinant human erythropoietin.”

jensmith@mdedge.com

Three researchers have won the 2019 Nobel Prize in Physiology or Medicine “for their discoveries of how cells sense and adapt to oxygen availability.”

William G. Kaelin Jr., MD; Sir Peter J. Ratcliffe, MB ChB, MD; and Gregg L. Semenza, MD, PhD, described the molecular machinery that regulates gene activity in response to oxygen levels.


Their work “established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function” and “paved the way for promising new strategies to fight anemia, cancer, and many other diseases,” according to a statement by The Nobel Assembly at Karolinska Institutet.

Dr. Semenza, of Johns Hopkins Medicine in Baltimore, studied how the erythropoietin (EPO) gene is regulated by oxygen levels. Via experiments in mice, he identified DNA segments next to the EPO gene that mediate the response to hypoxia.

Dr. Ratcliffe, of the University of Oxford (England) and the Francis Crick Institute in London, also studied oxygen-dependent regulation of the EPO gene. Both his and Dr. Semenza’s groups found the oxygen-sensing mechanism was present in nearly all tissues.

Dr. Kaelin, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, was researching von Hippel-Lindau’s (VHL) syndrome, an inherited disorder in which mutations can lead to tumors in multiple organs. He found the VHL gene encodes a protein that prevents cancer onset, and cancer cells without a functional VHL gene express high levels of hypoxia-regulated genes.

Research by other groups showed that VHL is part of a complex that labels proteins with ubiquitin, tagging them for degradation. Dr. Ratcliffe and his group found that VHL is required for the degradation of HIF-1a at normal oxygen levels.

Dr. Kaelin’s and Dr. Ratcliffe’s groups also showed that, under normal oxygen conditions, hydroxyl groups are added at two locations in HIF-1a. This modification – prolyl hydroxylation – allows VHL to bind to HIF-1a. So the researchers found that normal oxygen levels control HIF-1a degradation with the help of prolyl hydroxylases.

Additional research by Dr. Ratcliffe’s group and others revealed the specific prolyl hydroxylases involved in HIF-1a degradation. The researchers also found that HIF-1a’s gene-activating function was regulated by oxygen-dependent hydroxylation.

This work has improved the understanding of how different oxygen levels regulate physiological processes. In particular, oxygen sensing is essential for erythropoiesis, so these findings have implications for the treatment of anemia.

“There are several drugs that are now in clinical trials that serve to increase HIF activity and, as a result, will increase the production of erythropoietin and stimulate red blood cell production,” Dr. Semenza said in an interview after the announcement of his Nobel win. “These are all small molecules that can be given by mouth, and that may be a great convenience for patients who, at the present time, may require injections of recombinant human erythropoietin.”

jensmith@mdedge.com

ROCKVILLE, MD – Those suffering from rare diseases could see treatments being developed at a faster pace thanks to a research tool developed by the National Organization for Rare Disorders (NORD) and the Critical Path Institute (C-Path). Developed with grant money from the Food and Drug Administration, the platform, currently named the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), is designed to “promote the sharing of existing patient level data and encourage the standardization of new data collection,” according to information provided at a launch event held Sept. 18, 2019.

By integrating data in a regulatory-grade format suitable for analytics, the RDCA-DAP hopes to accelerate the understanding of disease progression – including source of variability to optimize the characterization of subpopulations – develop clinical outcome measures and biomarkers, facilitate the development of mathematical models of disease, and promote innovative clinical trial designs.

The RDCA-DAP works as a database that will house patient-level data from a variety of sources, including clinical trials, longitudinal observational studies, patient registries, and other sources, such as real-world data collected from electronic health records across a wide range of rare diseases from all over the world. Data will then be made available to researchers to help speed the development of new treatments.

“The database and analytics we are creating will enable us to obtain new insight into these rare diseases,” C-Path President and CEO Joseph Scheeren, PharmD, said at the launch event. “Not only within specific diseases, but also we hope across related diseases.”

Gregory Twachtman/MDedge News

The key to the platform’s success will be data. “We need access to clinical data from the industry, patient groups, and academia,” Dr. Scheeren said. “Even more so, the RDCA-DAP will need to incorporate data from many sources. In addition to data from clinical trials conducted by industry and academia, we will want to access data from patients, hospitals, and any organization that can provide data.”

Dr. Scheeren said the data will take many forms, including numeric data, images, genomic information, and other forms of clinical information.

“The database will be able to handle these diverse datasets,” he said, adding that C-Path is preparing to be able to analyze the data sets “with the most sophisticated tools available.”

Dr. Scheeren made a call for all interested stakeholders with rare disease data to contribute to the platform.

Gregory Twachtman/MDedge News

NORD President and CEO Peter Saltonstall echoed that call. “We need data. We are accepting it immediately.”

Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, applauded the new platform. “I think foundations and patient advocacy groups and others that have been trying to help in this space have realized that simply funding basic research, although it is necessary and really important, it is not enough to get those therapies in the hands of doctors and patients,” she said. “You have to enable translation of research for that disease.”

gtwachtman@mdedge.com

ROCKVILLE, MD – Those suffering from rare diseases could see treatments being developed at a faster pace thanks to a research tool developed by the National Organization for Rare Disorders (NORD) and the Critical Path Institute (C-Path). Developed with grant money from the Food and Drug Administration, the platform, currently named the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), is designed to “promote the sharing of existing patient level data and encourage the standardization of new data collection,” according to information provided at a launch event held Sept. 18, 2019.

By integrating data in a regulatory-grade format suitable for analytics, the RDCA-DAP hopes to accelerate the understanding of disease progression – including source of variability to optimize the characterization of subpopulations – develop clinical outcome measures and biomarkers, facilitate the development of mathematical models of disease, and promote innovative clinical trial designs.

The RDCA-DAP works as a database that will house patient-level data from a variety of sources, including clinical trials, longitudinal observational studies, patient registries, and other sources, such as real-world data collected from electronic health records across a wide range of rare diseases from all over the world. Data will then be made available to researchers to help speed the development of new treatments.

“The database and analytics we are creating will enable us to obtain new insight into these rare diseases,” C-Path President and CEO Joseph Scheeren, PharmD, said at the launch event. “Not only within specific diseases, but also we hope across related diseases.”

Gregory Twachtman/MDedge News

The key to the platform’s success will be data. “We need access to clinical data from the industry, patient groups, and academia,” Dr. Scheeren said. “Even more so, the RDCA-DAP will need to incorporate data from many sources. In addition to data from clinical trials conducted by industry and academia, we will want to access data from patients, hospitals, and any organization that can provide data.”

Dr. Scheeren said the data will take many forms, including numeric data, images, genomic information, and other forms of clinical information.

“The database will be able to handle these diverse datasets,” he said, adding that C-Path is preparing to be able to analyze the data sets “with the most sophisticated tools available.”

Dr. Scheeren made a call for all interested stakeholders with rare disease data to contribute to the platform.

Gregory Twachtman/MDedge News

NORD President and CEO Peter Saltonstall echoed that call. “We need data. We are accepting it immediately.”

Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, applauded the new platform. “I think foundations and patient advocacy groups and others that have been trying to help in this space have realized that simply funding basic research, although it is necessary and really important, it is not enough to get those therapies in the hands of doctors and patients,” she said. “You have to enable translation of research for that disease.”

gtwachtman@mdedge.com

ROCKVILLE, MD – Those suffering from rare diseases could see treatments being developed at a faster pace thanks to a research tool developed by the National Organization for Rare Disorders (NORD) and the Critical Path Institute (C-Path). Developed with grant money from the Food and Drug Administration, the platform, currently named the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), is designed to “promote the sharing of existing patient level data and encourage the standardization of new data collection,” according to information provided at a launch event held Sept. 18, 2019.

By integrating data in a regulatory-grade format suitable for analytics, the RDCA-DAP hopes to accelerate the understanding of disease progression – including source of variability to optimize the characterization of subpopulations – develop clinical outcome measures and biomarkers, facilitate the development of mathematical models of disease, and promote innovative clinical trial designs.

The RDCA-DAP works as a database that will house patient-level data from a variety of sources, including clinical trials, longitudinal observational studies, patient registries, and other sources, such as real-world data collected from electronic health records across a wide range of rare diseases from all over the world. Data will then be made available to researchers to help speed the development of new treatments.

“The database and analytics we are creating will enable us to obtain new insight into these rare diseases,” C-Path President and CEO Joseph Scheeren, PharmD, said at the launch event. “Not only within specific diseases, but also we hope across related diseases.”

Gregory Twachtman/MDedge News

The key to the platform’s success will be data. “We need access to clinical data from the industry, patient groups, and academia,” Dr. Scheeren said. “Even more so, the RDCA-DAP will need to incorporate data from many sources. In addition to data from clinical trials conducted by industry and academia, we will want to access data from patients, hospitals, and any organization that can provide data.”

Dr. Scheeren said the data will take many forms, including numeric data, images, genomic information, and other forms of clinical information.

“The database will be able to handle these diverse datasets,” he said, adding that C-Path is preparing to be able to analyze the data sets “with the most sophisticated tools available.”

Dr. Scheeren made a call for all interested stakeholders with rare disease data to contribute to the platform.

Gregory Twachtman/MDedge News

NORD President and CEO Peter Saltonstall echoed that call. “We need data. We are accepting it immediately.”

Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, applauded the new platform. “I think foundations and patient advocacy groups and others that have been trying to help in this space have realized that simply funding basic research, although it is necessary and really important, it is not enough to get those therapies in the hands of doctors and patients,” she said. “You have to enable translation of research for that disease.”

gtwachtman@mdedge.com

Click here to access Federal Health Care Cancer Data Trends 2019

Table of Contents

• Introduction
• Cancer in the VA: The Big Picture
• Hepatocellular Carcinoma
• Prostate Cancer
• Multiple Myeloma
• Lung Cancer in the VA at a National Level
• Lung Cancer – Regional Snapshot: Kansas City VA
• Colorectal Cancer
• Leukemias
• Lymphomas
• Renal Cell Carcinoma
• Bladder Cancer
• Afterword

Click here to access Federal Health Care Cancer Data Trends 2019

Table of Contents

• Introduction
• Cancer in the VA: The Big Picture
• Hepatocellular Carcinoma
• Prostate Cancer
• Multiple Myeloma
• Lung Cancer in the VA at a National Level
• Lung Cancer – Regional Snapshot: Kansas City VA
• Colorectal Cancer
• Leukemias
• Lymphomas
• Renal Cell Carcinoma
• Bladder Cancer
• Afterword

Click here to access Federal Health Care Cancer Data Trends 2019

Table of Contents

• Introduction
• Cancer in the VA: The Big Picture
• Hepatocellular Carcinoma
• Prostate Cancer
• Multiple Myeloma
• Lung Cancer in the VA at a National Level
• Lung Cancer – Regional Snapshot: Kansas City VA
• Colorectal Cancer
• Leukemias
• Lymphomas
• Renal Cell Carcinoma
• Bladder Cancer
• Afterword

CHICAGO – Surgery and endovascular treatment for peripheral artery disease (PAD) among patients with claudication improves health status more in the setting of isolated iliac disease and multilevel disease than in other forms of PAD, which suggests that vascular specialists should give pause before pursuing interventions on superficial femoral and infrapopliteal artery lesions, a researcher of the PORTRAIT registry reported at the annual meeting of the Midwestern Vascular Surgery Society.

“Our analysis demonstrated that interventions for aortoiliac disease and multilevel disease appeared to improve overall health status more over time compared to femoral-popliteal disease and infrapopliteal disease,” said Todd R. Vogel, MD, of the University of Missouri Health System in Columbia.

The study evaluated improvement in Peripheral Artery Questionnaire (PAQ) scores from baseline to post intervention in 623 patients in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry. The patients were selected and combined with anatomic data on the nature of their claudication. Aortoiliac-only (AI) disease represented 20.4% (n = 127) of the study group, femoral-popliteal-only (FP) 35.5% (n = 221), infrapopliteal/distal (IP) 6.3% (n = 39), and multilevel disease (ML) 37.9% (n = 236).

In terms of demographics, patients in the AI group tended to be younger (average age of 61.2 years vs. 66.6 years for the study overall; P less than .001) and had a higher rate of smokers (96.1% former and current smokers vs. 90.7% overall; P less than .001). Otherwise, Dr. Vogel noted, demographics, smoking status, and severity of claudication were similar across the disease groups.

Rates of medical intervention were similar in the AI and ML disease groups, which were primarily endovascular procedures: 26% and 27%, respectively. The AI group had the highest rates of endovascular interventions, at 24%, with the FP group at 15%, IP at 11% and ML at 21%. Those who did not have surgery or endovascular aneurysm repair were treated medically.

“The AI group did significantly better at 3 months than the other groups,” Dr. Vogel pointed out, noting that at 12 months those patients had an average PAQ score of around 78 versus scores of around 75 for FP, 74 for IP, and 70 for ML.

“In the AI group, there’s also an immediate increase in quality of life that is sustained over time,” he said. At 3 months, PAQ scores in AI patients who had endovascular aneurysm repair increased 41 points over baseline, leveling off to a 38.8-point gain at 12 months, the highest gains across all disease groups and all treatment categories.

“However,” Dr. Vogel added, “the group with ML disease probably was the most improved over time on the PAQ scores,” he said, explaining that across the board, this group had lower baseline PAQ scores than all the other groups.

“No significant benefits were found with intervention versus medical management for FP and IP,” he said. “This suggests that intervention should be considered after medical management has been exhausted.”

Dr. Vogel also said the findings support aggressive treatment of AI and ML for symptomatic claudication. “This anatomic region represents the greatest potential benefit for improving overall health status in patients with symptomatic PAD,” he said.

Dr. Vogel had no relevant financial relationships to disclose.

CHICAGO – Surgery and endovascular treatment for peripheral artery disease (PAD) among patients with claudication improves health status more in the setting of isolated iliac disease and multilevel disease than in other forms of PAD, which suggests that vascular specialists should give pause before pursuing interventions on superficial femoral and infrapopliteal artery lesions, a researcher of the PORTRAIT registry reported at the annual meeting of the Midwestern Vascular Surgery Society.

“Our analysis demonstrated that interventions for aortoiliac disease and multilevel disease appeared to improve overall health status more over time compared to femoral-popliteal disease and infrapopliteal disease,” said Todd R. Vogel, MD, of the University of Missouri Health System in Columbia.

The study evaluated improvement in Peripheral Artery Questionnaire (PAQ) scores from baseline to post intervention in 623 patients in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry. The patients were selected and combined with anatomic data on the nature of their claudication. Aortoiliac-only (AI) disease represented 20.4% (n = 127) of the study group, femoral-popliteal-only (FP) 35.5% (n = 221), infrapopliteal/distal (IP) 6.3% (n = 39), and multilevel disease (ML) 37.9% (n = 236).

In terms of demographics, patients in the AI group tended to be younger (average age of 61.2 years vs. 66.6 years for the study overall; P less than .001) and had a higher rate of smokers (96.1% former and current smokers vs. 90.7% overall; P less than .001). Otherwise, Dr. Vogel noted, demographics, smoking status, and severity of claudication were similar across the disease groups.

Rates of medical intervention were similar in the AI and ML disease groups, which were primarily endovascular procedures: 26% and 27%, respectively. The AI group had the highest rates of endovascular interventions, at 24%, with the FP group at 15%, IP at 11% and ML at 21%. Those who did not have surgery or endovascular aneurysm repair were treated medically.

“The AI group did significantly better at 3 months than the other groups,” Dr. Vogel pointed out, noting that at 12 months those patients had an average PAQ score of around 78 versus scores of around 75 for FP, 74 for IP, and 70 for ML.

“In the AI group, there’s also an immediate increase in quality of life that is sustained over time,” he said. At 3 months, PAQ scores in AI patients who had endovascular aneurysm repair increased 41 points over baseline, leveling off to a 38.8-point gain at 12 months, the highest gains across all disease groups and all treatment categories.

“However,” Dr. Vogel added, “the group with ML disease probably was the most improved over time on the PAQ scores,” he said, explaining that across the board, this group had lower baseline PAQ scores than all the other groups.

“No significant benefits were found with intervention versus medical management for FP and IP,” he said. “This suggests that intervention should be considered after medical management has been exhausted.”

Dr. Vogel also said the findings support aggressive treatment of AI and ML for symptomatic claudication. “This anatomic region represents the greatest potential benefit for improving overall health status in patients with symptomatic PAD,” he said.

Dr. Vogel had no relevant financial relationships to disclose.

CHICAGO – Surgery and endovascular treatment for peripheral artery disease (PAD) among patients with claudication improves health status more in the setting of isolated iliac disease and multilevel disease than in other forms of PAD, which suggests that vascular specialists should give pause before pursuing interventions on superficial femoral and infrapopliteal artery lesions, a researcher of the PORTRAIT registry reported at the annual meeting of the Midwestern Vascular Surgery Society.

“Our analysis demonstrated that interventions for aortoiliac disease and multilevel disease appeared to improve overall health status more over time compared to femoral-popliteal disease and infrapopliteal disease,” said Todd R. Vogel, MD, of the University of Missouri Health System in Columbia.

The study evaluated improvement in Peripheral Artery Questionnaire (PAQ) scores from baseline to post intervention in 623 patients in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry. The patients were selected and combined with anatomic data on the nature of their claudication. Aortoiliac-only (AI) disease represented 20.4% (n = 127) of the study group, femoral-popliteal-only (FP) 35.5% (n = 221), infrapopliteal/distal (IP) 6.3% (n = 39), and multilevel disease (ML) 37.9% (n = 236).

In terms of demographics, patients in the AI group tended to be younger (average age of 61.2 years vs. 66.6 years for the study overall; P less than .001) and had a higher rate of smokers (96.1% former and current smokers vs. 90.7% overall; P less than .001). Otherwise, Dr. Vogel noted, demographics, smoking status, and severity of claudication were similar across the disease groups.

Rates of medical intervention were similar in the AI and ML disease groups, which were primarily endovascular procedures: 26% and 27%, respectively. The AI group had the highest rates of endovascular interventions, at 24%, with the FP group at 15%, IP at 11% and ML at 21%. Those who did not have surgery or endovascular aneurysm repair were treated medically.

“The AI group did significantly better at 3 months than the other groups,” Dr. Vogel pointed out, noting that at 12 months those patients had an average PAQ score of around 78 versus scores of around 75 for FP, 74 for IP, and 70 for ML.

“In the AI group, there’s also an immediate increase in quality of life that is sustained over time,” he said. At 3 months, PAQ scores in AI patients who had endovascular aneurysm repair increased 41 points over baseline, leveling off to a 38.8-point gain at 12 months, the highest gains across all disease groups and all treatment categories.

“However,” Dr. Vogel added, “the group with ML disease probably was the most improved over time on the PAQ scores,” he said, explaining that across the board, this group had lower baseline PAQ scores than all the other groups.

“No significant benefits were found with intervention versus medical management for FP and IP,” he said. “This suggests that intervention should be considered after medical management has been exhausted.”

Dr. Vogel also said the findings support aggressive treatment of AI and ML for symptomatic claudication. “This anatomic region represents the greatest potential benefit for improving overall health status in patients with symptomatic PAD,” he said.

Dr. Vogel had no relevant financial relationships to disclose.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.