Mitchel L. Zoler, PhD

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

"The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy," Dr. Carlo B. Ramirez said at the American Transplant Congress. "The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child," said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.

Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

"A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy" that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years old among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.

The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

"The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy," Dr. Carlo B. Ramirez said at the American Transplant Congress. "The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child," said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.

Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

"A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy" that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years old among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.

The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

"The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy," Dr. Carlo B. Ramirez said at the American Transplant Congress. "The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child," said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.

Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

"A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy" that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years old among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.

The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

PHILADELPHIA – A blood glucose target of 121-180 mg/dL for patients following isolated coronary bypass surgery was as clinically effective as was a stricter glucose target and was easier to maintain in a randomized study with 189 patients.

Based on these results, the cardiac surgery program that ran the study switched its blood glucose range for postoperative patients from 90-120 mg/dL to the more liberal range of 121-180 mg/dL, Dr. Shalin P. Desai said at the annual meeting of the American Association for Thoracic Surgery.

"We believe that maintaining patients at a blood glucose level less than 180 mg/dL is safe and effective, and therefore should be considered for patients undergoing coronary artery bypass grafting surgery," said Dr. Desai, a cardiac surgeon at Inova Heart and Vascular Institute in Falls Church, Va.

"We know that a glucose level of less than 180 mg/dL is good, but does it need to be so strict that it’s almost normoglycemic, or can it be more liberal when we know the glucose levels will rise with the stress of surgery and illness? A range of 121-180 mg/dL is probably sufficient," Dr. Desai said in an interview. At that level, "we used less insulin, fewer finger sticks, and fewer resources" than when the target range aims for lower blood glucose levels, he said.

Dr. Desai and his associates enrolled patients undergoing first-time, isolated CABG who had diabetes or required insulin treatment following surgery based on having three consecutive blood glucose readings of at least 150 mg/dL, or one reading of at least 200 mg/dL. The researchers used a bedside, computerized device that regularly assessed blood glucose levels and adjusted the insulin infusion accordingly. The patients averaged 62 years of age, and about 43% had diabetes.

Among the 98 patients maintained on the 121-180 mg/dL regimen, the average time needed to reach the target blood glucose range was 84 minutes – significantly shorter than the average 173 minutes needed for the 91 patients on the strict regimen.

Patients maintained on the liberal target also fared significantly better in their average number of readings within their target range, minimum glucose level, number of hypoglycemic readings, and total insulin dose received (see table).

Assessment of clinical outcomes – renal failure, atrial fibrillation, pneumonia, deep sternal wound infections, prolonged ventilation, prolonged hospitalization, and operative mortality – showed that the liberal range was not inferior to the strict range for preventing these complications in the primary, intention-to-treat analysis. In the as-treated and per-protocol analyses, the liberal-range patients had outcomes that were noninferior to those of the strict control patients for all parameters except for atrial fibrillation. The liberal-range patients showed a small excess of atrial fibrillations in these two additional analyses.

Future studies should look at the same issue in patients undergoing other types of cardiac surgery, such as valve repair or replacement, or a maze procedure, he said.

Dr. Desai said that he had no relevant financial disclosures.

PHILADELPHIA – A blood glucose target of 121-180 mg/dL for patients following isolated coronary bypass surgery was as clinically effective as was a stricter glucose target and was easier to maintain in a randomized study with 189 patients.

Based on these results, the cardiac surgery program that ran the study switched its blood glucose range for postoperative patients from 90-120 mg/dL to the more liberal range of 121-180 mg/dL, Dr. Shalin P. Desai said at the annual meeting of the American Association for Thoracic Surgery.

"We believe that maintaining patients at a blood glucose level less than 180 mg/dL is safe and effective, and therefore should be considered for patients undergoing coronary artery bypass grafting surgery," said Dr. Desai, a cardiac surgeon at Inova Heart and Vascular Institute in Falls Church, Va.

"We know that a glucose level of less than 180 mg/dL is good, but does it need to be so strict that it’s almost normoglycemic, or can it be more liberal when we know the glucose levels will rise with the stress of surgery and illness? A range of 121-180 mg/dL is probably sufficient," Dr. Desai said in an interview. At that level, "we used less insulin, fewer finger sticks, and fewer resources" than when the target range aims for lower blood glucose levels, he said.

Dr. Desai and his associates enrolled patients undergoing first-time, isolated CABG who had diabetes or required insulin treatment following surgery based on having three consecutive blood glucose readings of at least 150 mg/dL, or one reading of at least 200 mg/dL. The researchers used a bedside, computerized device that regularly assessed blood glucose levels and adjusted the insulin infusion accordingly. The patients averaged 62 years of age, and about 43% had diabetes.

Among the 98 patients maintained on the 121-180 mg/dL regimen, the average time needed to reach the target blood glucose range was 84 minutes – significantly shorter than the average 173 minutes needed for the 91 patients on the strict regimen.

Patients maintained on the liberal target also fared significantly better in their average number of readings within their target range, minimum glucose level, number of hypoglycemic readings, and total insulin dose received (see table).

Assessment of clinical outcomes – renal failure, atrial fibrillation, pneumonia, deep sternal wound infections, prolonged ventilation, prolonged hospitalization, and operative mortality – showed that the liberal range was not inferior to the strict range for preventing these complications in the primary, intention-to-treat analysis. In the as-treated and per-protocol analyses, the liberal-range patients had outcomes that were noninferior to those of the strict control patients for all parameters except for atrial fibrillation. The liberal-range patients showed a small excess of atrial fibrillations in these two additional analyses.

Future studies should look at the same issue in patients undergoing other types of cardiac surgery, such as valve repair or replacement, or a maze procedure, he said.

Dr. Desai said that he had no relevant financial disclosures.

PHILADELPHIA – A blood glucose target of 121-180 mg/dL for patients following isolated coronary bypass surgery was as clinically effective as was a stricter glucose target and was easier to maintain in a randomized study with 189 patients.

Based on these results, the cardiac surgery program that ran the study switched its blood glucose range for postoperative patients from 90-120 mg/dL to the more liberal range of 121-180 mg/dL, Dr. Shalin P. Desai said at the annual meeting of the American Association for Thoracic Surgery.

"We believe that maintaining patients at a blood glucose level less than 180 mg/dL is safe and effective, and therefore should be considered for patients undergoing coronary artery bypass grafting surgery," said Dr. Desai, a cardiac surgeon at Inova Heart and Vascular Institute in Falls Church, Va.

"We know that a glucose level of less than 180 mg/dL is good, but does it need to be so strict that it’s almost normoglycemic, or can it be more liberal when we know the glucose levels will rise with the stress of surgery and illness? A range of 121-180 mg/dL is probably sufficient," Dr. Desai said in an interview. At that level, "we used less insulin, fewer finger sticks, and fewer resources" than when the target range aims for lower blood glucose levels, he said.

Dr. Desai and his associates enrolled patients undergoing first-time, isolated CABG who had diabetes or required insulin treatment following surgery based on having three consecutive blood glucose readings of at least 150 mg/dL, or one reading of at least 200 mg/dL. The researchers used a bedside, computerized device that regularly assessed blood glucose levels and adjusted the insulin infusion accordingly. The patients averaged 62 years of age, and about 43% had diabetes.

Among the 98 patients maintained on the 121-180 mg/dL regimen, the average time needed to reach the target blood glucose range was 84 minutes – significantly shorter than the average 173 minutes needed for the 91 patients on the strict regimen.

Patients maintained on the liberal target also fared significantly better in their average number of readings within their target range, minimum glucose level, number of hypoglycemic readings, and total insulin dose received (see table).

Assessment of clinical outcomes – renal failure, atrial fibrillation, pneumonia, deep sternal wound infections, prolonged ventilation, prolonged hospitalization, and operative mortality – showed that the liberal range was not inferior to the strict range for preventing these complications in the primary, intention-to-treat analysis. In the as-treated and per-protocol analyses, the liberal-range patients had outcomes that were noninferior to those of the strict control patients for all parameters except for atrial fibrillation. The liberal-range patients showed a small excess of atrial fibrillations in these two additional analyses.

Future studies should look at the same issue in patients undergoing other types of cardiac surgery, such as valve repair or replacement, or a maze procedure, he said.

Dr. Desai said that he had no relevant financial disclosures.

PHILADELPHIA – A blood glucose target of 121-180 mg/dL for patients following isolated coronary bypass surgery was as clinically effective as was a stricter glucose target and was easier to maintain in a randomized study with 189 patients.

Based on these results, the cardiac surgery program that ran the study switched its blood glucose range for postoperative patients from 90-120 mg/dL to the more liberal range of 121-180 mg/dL, Dr. Shalin P. Desai said at the annual meeting of the American Association for Thoracic Surgery.

"We believe that maintaining patients at a blood glucose level less than 180 mg/dL is safe and effective, and therefore should be considered for patients undergoing coronary artery bypass grafting surgery," said Dr. Desai, a cardiac surgeon at Inova Heart and Vascular Institute in Falls Church, Va.

"We know that a glucose level of less than 180 mg/dL is good, but does it need to be so strict that it’s almost normoglycemic, or can it be more liberal when we know the glucose levels will rise with the stress of surgery and illness? A range of 121-180 mg/dL is probably sufficient," Dr. Desai said in an interview. At that level, "we used less insulin, fewer finger sticks, and fewer resources" than when the target range aims for lower blood glucose levels, he said.

Dr. Desai and his associates enrolled patients undergoing first-time, isolated CABG who had diabetes or required insulin treatment following surgery based on having three consecutive blood glucose readings of at least 150 mg/dL, or one reading of at least 200 mg/dL. The researchers used a bedside, computerized device that regularly assessed blood glucose levels and adjusted the insulin infusion accordingly. The patients averaged 62 years of age, and about 43% had diabetes.

Among the 98 patients maintained on the 121-180 mg/dL regimen, the average time needed to reach the target blood glucose range was 84 minutes – significantly shorter than the average 173 minutes needed for the 91 patients on the strict regimen.

Patients maintained on the liberal target also fared significantly better in their average number of readings within their target range, minimum glucose level, number of hypoglycemic readings, and total insulin dose received (see table).

Assessment of clinical outcomes – renal failure, atrial fibrillation, pneumonia, deep sternal wound infections, prolonged ventilation, prolonged hospitalization, and operative mortality – showed that the liberal range was not inferior to the strict range for preventing these complications in the primary, intention-to-treat analysis. In the as-treated and per-protocol analyses, the liberal-range patients had outcomes that were noninferior to those of the strict control patients for all parameters except for atrial fibrillation. The liberal-range patients showed a small excess of atrial fibrillations in these two additional analyses.

Future studies should look at the same issue in patients undergoing other types of cardiac surgery, such as valve repair or replacement, or a maze procedure, he said.

Dr. Desai said that he had no relevant financial disclosures.

PHILADELPHIA – A blood glucose target of 121-180 mg/dL for patients following isolated coronary bypass surgery was as clinically effective as was a stricter glucose target and was easier to maintain in a randomized study with 189 patients.

Based on these results, the cardiac surgery program that ran the study switched its blood glucose range for postoperative patients from 90-120 mg/dL to the more liberal range of 121-180 mg/dL, Dr. Shalin P. Desai said at the annual meeting of the American Association for Thoracic Surgery.

"We believe that maintaining patients at a blood glucose level less than 180 mg/dL is safe and effective, and therefore should be considered for patients undergoing coronary artery bypass grafting surgery," said Dr. Desai, a cardiac surgeon at Inova Heart and Vascular Institute in Falls Church, Va.

"We know that a glucose level of less than 180 mg/dL is good, but does it need to be so strict that it’s almost normoglycemic, or can it be more liberal when we know the glucose levels will rise with the stress of surgery and illness? A range of 121-180 mg/dL is probably sufficient," Dr. Desai said in an interview. At that level, "we used less insulin, fewer finger sticks, and fewer resources" than when the target range aims for lower blood glucose levels, he said.

Dr. Desai and his associates enrolled patients undergoing first-time, isolated CABG who had diabetes or required insulin treatment following surgery based on having three consecutive blood glucose readings of at least 150 mg/dL, or one reading of at least 200 mg/dL. The researchers used a bedside, computerized device that regularly assessed blood glucose levels and adjusted the insulin infusion accordingly. The patients averaged 62 years of age, and about 43% had diabetes.

Among the 98 patients maintained on the 121-180 mg/dL regimen, the average time needed to reach the target blood glucose range was 84 minutes – significantly shorter than the average 173 minutes needed for the 91 patients on the strict regimen.

Patients maintained on the liberal target also fared significantly better in their average number of readings within their target range, minimum glucose level, number of hypoglycemic readings, and total insulin dose received (see table).

Assessment of clinical outcomes – renal failure, atrial fibrillation, pneumonia, deep sternal wound infections, prolonged ventilation, prolonged hospitalization, and operative mortality – showed that the liberal range was not inferior to the strict range for preventing these complications in the primary, intention-to-treat analysis. In the as-treated and per-protocol analyses, the liberal-range patients had outcomes that were noninferior to those of the strict control patients for all parameters except for atrial fibrillation. The liberal-range patients showed a small excess of atrial fibrillations in these two additional analyses.

Future studies should look at the same issue in patients undergoing other types of cardiac surgery, such as valve repair or replacement, or a maze procedure, he said.

Dr. Desai said that he had no relevant financial disclosures.

PHILADELPHIA – A blood glucose target of 121-180 mg/dL for patients following isolated coronary bypass surgery was as clinically effective as was a stricter glucose target and was easier to maintain in a randomized study with 189 patients.

Based on these results, the cardiac surgery program that ran the study switched its blood glucose range for postoperative patients from 90-120 mg/dL to the more liberal range of 121-180 mg/dL, Dr. Shalin P. Desai said at the annual meeting of the American Association for Thoracic Surgery.

"We believe that maintaining patients at a blood glucose level less than 180 mg/dL is safe and effective, and therefore should be considered for patients undergoing coronary artery bypass grafting surgery," said Dr. Desai, a cardiac surgeon at Inova Heart and Vascular Institute in Falls Church, Va.

"We know that a glucose level of less than 180 mg/dL is good, but does it need to be so strict that it’s almost normoglycemic, or can it be more liberal when we know the glucose levels will rise with the stress of surgery and illness? A range of 121-180 mg/dL is probably sufficient," Dr. Desai said in an interview. At that level, "we used less insulin, fewer finger sticks, and fewer resources" than when the target range aims for lower blood glucose levels, he said.

Dr. Desai and his associates enrolled patients undergoing first-time, isolated CABG who had diabetes or required insulin treatment following surgery based on having three consecutive blood glucose readings of at least 150 mg/dL, or one reading of at least 200 mg/dL. The researchers used a bedside, computerized device that regularly assessed blood glucose levels and adjusted the insulin infusion accordingly. The patients averaged 62 years of age, and about 43% had diabetes.

Among the 98 patients maintained on the 121-180 mg/dL regimen, the average time needed to reach the target blood glucose range was 84 minutes – significantly shorter than the average 173 minutes needed for the 91 patients on the strict regimen.

Patients maintained on the liberal target also fared significantly better in their average number of readings within their target range, minimum glucose level, number of hypoglycemic readings, and total insulin dose received (see table).

Assessment of clinical outcomes – renal failure, atrial fibrillation, pneumonia, deep sternal wound infections, prolonged ventilation, prolonged hospitalization, and operative mortality – showed that the liberal range was not inferior to the strict range for preventing these complications in the primary, intention-to-treat analysis. In the as-treated and per-protocol analyses, the liberal-range patients had outcomes that were noninferior to those of the strict control patients for all parameters except for atrial fibrillation. The liberal-range patients showed a small excess of atrial fibrillations in these two additional analyses.

Future studies should look at the same issue in patients undergoing other types of cardiac surgery, such as valve repair or replacement, or a maze procedure, he said.

Dr. Desai said that he had no relevant financial disclosures.

PHILADELPHIA – Endovascular repair may be better than open surgery for emergency treatment of patients with a thoracic aortic aneurysm rupture who receive care at smaller U.S. hospitals, based on an analysis of more than 900 patients treated during 2006-2008.

Investigators found that emergency thoracic endovascular aneurysm repair (TEVAR) led to a nearly 80% reduction in complications, compared with open surgical aneurysm repair, in patients who were treated at smaller U.S. hospitals. At larger hospitals, TEVAR and open repair produced similar outcomes, Dr. Raja R. Gopaldas said at the annual meeting of the American Association for Thoracic Surgery.

"TEVAR is an ideal alternative when transfer to a larger facility is not feasible," said Dr. Gopaldas, a cardiothoracic surgeon at the University of Missouri in Columbia.

"We were surprised when we saw that smaller hospitals had better outcomes with TEVAR, but it makes sense. A lot of hospitals lack expertise in open thoracic aortic repair because it requires a highly skilled surgeon, whereas a lot of small hospitals have a cardiac catheterization lab and a cardiologist or vascular surgeon available," he said in an interview. He added that open repair was more successful when performed at larger hospitals, but when TEVAR was used, results were similar.

Widespread availability of TEVAR catheter systems began in 2005. During 2006-2008, TEVAR was used in 40% of emergency thoracic aortic aneurysm repairs. Because these were the first 3 years after U.S. approval, such a high level of TEVAR use, especially in emergency circumstances, fell beyond Dr. Gopaldas’s expectations. "Forty percent is a huge number," he said.

The findings also suggested a role for "TEVAR first" in the emergency repair of ruptured thoracic aortic aneurysms, because the operative team often can intervene more quickly with an endovascular approach than with open surgical repair.

"I think there will be a lot of push to use the endovascular approach more frequently, because it is probably a lot quicker to set up your team," Dr. Gopaldas said. ""It’s quicker to get a TEVAR stent deployed than to cut open a patient’s chest. The endovascular team is probably geared to respond more quickly [than is] the open-heart surgical team in smaller hospitals. In bigger hospitals, there may not be as much of a difference."

The study used data collected by the Nationwide Inpatient Sample, an annual sampling of slightly more than 1,000 U.S. hospitals – about 20% of all U.S. patient discharge records – done by the Agency for Healthcare Research and Quality. Using data for 2006-2008, Dr. Gopaldas and his associates identified 923 patients who underwent emergency repair of a thoracic aortic aneurysm at one of 107 hospitals that performed these repairs. Among those hospitals, 41 (38%) performed TEVAR.

The analysis also divided hospitals into smaller and larger hospitals based on bed numbers. The definition of "smaller" differed based on U.S. geographical region (Northeast, Midwest, South, or West), rural vs. urban, and teaching vs. nonteaching hospitals. The bed sizes of smaller hospitals ranged from 1 to 449 (an urban teaching hospital in the Southern region). Larger hospitals included any center with a bed number larger than the study definition of smaller. Among the 107 hospitals that performed TEVAR during the study period, 27 (25%) were smaller hospitals.

In a risk-adjusted analysis, patients who underwent open surgical repair at a smaller hospital had a threefold increased risk for a subsequent complication, compared with patients treated by surgery at a larger hospital. But among the patients treated with TEVAR, the outcomes at smaller hospitals matched those that were achieved at larger hospitals. A comparison of open surgery and TEVAR outcomes within smaller hospitals showed that TEVAR led to a 79% lower complication rate, Dr. Gopaldas reported. In larger hospitals, outcomes were similar for patients treated with open surgery vs. TEVAR.

The risk-adjusted analysis also showed that once patients developed complications, they fared worse in smaller hospitals regardless of the type of aneurysm repair they received. Smaller hospitals had a failure-to-rescue rate that was nearly fourfold higher than that of larger hospitals. By lowering complication rates, TEVAR proved especially advantageous in smaller hospitals, Dr. Gopaldas said. He did these analyses in collaboration with researchers from Baylor College of Medicine and the Texas Heart Institute, also in Houston.

Dr. Gopaldas said that he had no relevant financial disclosures.

PHILADELPHIA – Endovascular repair may be better than open surgery for emergency treatment of patients with a thoracic aortic aneurysm rupture who receive care at smaller U.S. hospitals, based on an analysis of more than 900 patients treated during 2006-2008.

Investigators found that emergency thoracic endovascular aneurysm repair (TEVAR) led to a nearly 80% reduction in complications, compared with open surgical aneurysm repair, in patients who were treated at smaller U.S. hospitals. At larger hospitals, TEVAR and open repair produced similar outcomes, Dr. Raja R. Gopaldas said at the annual meeting of the American Association for Thoracic Surgery.

"TEVAR is an ideal alternative when transfer to a larger facility is not feasible," said Dr. Gopaldas, a cardiothoracic surgeon at the University of Missouri in Columbia.

"We were surprised when we saw that smaller hospitals had better outcomes with TEVAR, but it makes sense. A lot of hospitals lack expertise in open thoracic aortic repair because it requires a highly skilled surgeon, whereas a lot of small hospitals have a cardiac catheterization lab and a cardiologist or vascular surgeon available," he said in an interview. He added that open repair was more successful when performed at larger hospitals, but when TEVAR was used, results were similar.

Widespread availability of TEVAR catheter systems began in 2005. During 2006-2008, TEVAR was used in 40% of emergency thoracic aortic aneurysm repairs. Because these were the first 3 years after U.S. approval, such a high level of TEVAR use, especially in emergency circumstances, fell beyond Dr. Gopaldas’s expectations. "Forty percent is a huge number," he said.

The findings also suggested a role for "TEVAR first" in the emergency repair of ruptured thoracic aortic aneurysms, because the operative team often can intervene more quickly with an endovascular approach than with open surgical repair.

"I think there will be a lot of push to use the endovascular approach more frequently, because it is probably a lot quicker to set up your team," Dr. Gopaldas said. ""It’s quicker to get a TEVAR stent deployed than to cut open a patient’s chest. The endovascular team is probably geared to respond more quickly [than is] the open-heart surgical team in smaller hospitals. In bigger hospitals, there may not be as much of a difference."

The study used data collected by the Nationwide Inpatient Sample, an annual sampling of slightly more than 1,000 U.S. hospitals – about 20% of all U.S. patient discharge records – done by the Agency for Healthcare Research and Quality. Using data for 2006-2008, Dr. Gopaldas and his associates identified 923 patients who underwent emergency repair of a thoracic aortic aneurysm at one of 107 hospitals that performed these repairs. Among those hospitals, 41 (38%) performed TEVAR.

The analysis also divided hospitals into smaller and larger hospitals based on bed numbers. The definition of "smaller" differed based on U.S. geographical region (Northeast, Midwest, South, or West), rural vs. urban, and teaching vs. nonteaching hospitals. The bed sizes of smaller hospitals ranged from 1 to 449 (an urban teaching hospital in the Southern region). Larger hospitals included any center with a bed number larger than the study definition of smaller. Among the 107 hospitals that performed TEVAR during the study period, 27 (25%) were smaller hospitals.

In a risk-adjusted analysis, patients who underwent open surgical repair at a smaller hospital had a threefold increased risk for a subsequent complication, compared with patients treated by surgery at a larger hospital. But among the patients treated with TEVAR, the outcomes at smaller hospitals matched those that were achieved at larger hospitals. A comparison of open surgery and TEVAR outcomes within smaller hospitals showed that TEVAR led to a 79% lower complication rate, Dr. Gopaldas reported. In larger hospitals, outcomes were similar for patients treated with open surgery vs. TEVAR.

The risk-adjusted analysis also showed that once patients developed complications, they fared worse in smaller hospitals regardless of the type of aneurysm repair they received. Smaller hospitals had a failure-to-rescue rate that was nearly fourfold higher than that of larger hospitals. By lowering complication rates, TEVAR proved especially advantageous in smaller hospitals, Dr. Gopaldas said. He did these analyses in collaboration with researchers from Baylor College of Medicine and the Texas Heart Institute, also in Houston.

Dr. Gopaldas said that he had no relevant financial disclosures.

PHILADELPHIA – Endovascular repair may be better than open surgery for emergency treatment of patients with a thoracic aortic aneurysm rupture who receive care at smaller U.S. hospitals, based on an analysis of more than 900 patients treated during 2006-2008.

Investigators found that emergency thoracic endovascular aneurysm repair (TEVAR) led to a nearly 80% reduction in complications, compared with open surgical aneurysm repair, in patients who were treated at smaller U.S. hospitals. At larger hospitals, TEVAR and open repair produced similar outcomes, Dr. Raja R. Gopaldas said at the annual meeting of the American Association for Thoracic Surgery.

"TEVAR is an ideal alternative when transfer to a larger facility is not feasible," said Dr. Gopaldas, a cardiothoracic surgeon at the University of Missouri in Columbia.

"We were surprised when we saw that smaller hospitals had better outcomes with TEVAR, but it makes sense. A lot of hospitals lack expertise in open thoracic aortic repair because it requires a highly skilled surgeon, whereas a lot of small hospitals have a cardiac catheterization lab and a cardiologist or vascular surgeon available," he said in an interview. He added that open repair was more successful when performed at larger hospitals, but when TEVAR was used, results were similar.

Widespread availability of TEVAR catheter systems began in 2005. During 2006-2008, TEVAR was used in 40% of emergency thoracic aortic aneurysm repairs. Because these were the first 3 years after U.S. approval, such a high level of TEVAR use, especially in emergency circumstances, fell beyond Dr. Gopaldas’s expectations. "Forty percent is a huge number," he said.

The findings also suggested a role for "TEVAR first" in the emergency repair of ruptured thoracic aortic aneurysms, because the operative team often can intervene more quickly with an endovascular approach than with open surgical repair.

"I think there will be a lot of push to use the endovascular approach more frequently, because it is probably a lot quicker to set up your team," Dr. Gopaldas said. ""It’s quicker to get a TEVAR stent deployed than to cut open a patient’s chest. The endovascular team is probably geared to respond more quickly [than is] the open-heart surgical team in smaller hospitals. In bigger hospitals, there may not be as much of a difference."

The study used data collected by the Nationwide Inpatient Sample, an annual sampling of slightly more than 1,000 U.S. hospitals – about 20% of all U.S. patient discharge records – done by the Agency for Healthcare Research and Quality. Using data for 2006-2008, Dr. Gopaldas and his associates identified 923 patients who underwent emergency repair of a thoracic aortic aneurysm at one of 107 hospitals that performed these repairs. Among those hospitals, 41 (38%) performed TEVAR.

The analysis also divided hospitals into smaller and larger hospitals based on bed numbers. The definition of "smaller" differed based on U.S. geographical region (Northeast, Midwest, South, or West), rural vs. urban, and teaching vs. nonteaching hospitals. The bed sizes of smaller hospitals ranged from 1 to 449 (an urban teaching hospital in the Southern region). Larger hospitals included any center with a bed number larger than the study definition of smaller. Among the 107 hospitals that performed TEVAR during the study period, 27 (25%) were smaller hospitals.

In a risk-adjusted analysis, patients who underwent open surgical repair at a smaller hospital had a threefold increased risk for a subsequent complication, compared with patients treated by surgery at a larger hospital. But among the patients treated with TEVAR, the outcomes at smaller hospitals matched those that were achieved at larger hospitals. A comparison of open surgery and TEVAR outcomes within smaller hospitals showed that TEVAR led to a 79% lower complication rate, Dr. Gopaldas reported. In larger hospitals, outcomes were similar for patients treated with open surgery vs. TEVAR.

The risk-adjusted analysis also showed that once patients developed complications, they fared worse in smaller hospitals regardless of the type of aneurysm repair they received. Smaller hospitals had a failure-to-rescue rate that was nearly fourfold higher than that of larger hospitals. By lowering complication rates, TEVAR proved especially advantageous in smaller hospitals, Dr. Gopaldas said. He did these analyses in collaboration with researchers from Baylor College of Medicine and the Texas Heart Institute, also in Houston.

Dr. Gopaldas said that he had no relevant financial disclosures.

PHILADELPHIA – Endovascular repair may be better than open surgery for emergency treatment of patients with a thoracic aortic aneurysm rupture who receive care at smaller U.S. hospitals, based on an analysis of more than 900 patients treated during 2006-2008.

Investigators found that emergency thoracic endovascular aneurysm repair (TEVAR) led to a nearly 80% reduction in complications, compared with open surgical aneurysm repair, in patients who were treated at smaller U.S. hospitals. At larger hospitals, TEVAR and open repair produced similar outcomes, Dr. Raja R. Gopaldas said at the annual meeting of the American Association for Thoracic Surgery.

"TEVAR is an ideal alternative when transfer to a larger facility is not feasible," said Dr. Gopaldas, a cardiothoracic surgeon at the University of Missouri in Columbia.

"We were surprised when we saw that smaller hospitals had better outcomes with TEVAR, but it makes sense. A lot of hospitals lack expertise in open thoracic aortic repair because it requires a highly skilled surgeon, whereas a lot of small hospitals have a cardiac catheterization lab and a cardiologist or vascular surgeon available," he said in an interview. He added that open repair was more successful when performed at larger hospitals, but when TEVAR was used, results were similar.

Widespread availability of TEVAR catheter systems began in 2005. During 2006-2008, TEVAR was used in 40% of emergency thoracic aortic aneurysm repairs. Because these were the first 3 years after U.S. approval, such a high level of TEVAR use, especially in emergency circumstances, fell beyond Dr. Gopaldas’s expectations. "Forty percent is a huge number," he said.

The findings also suggested a role for "TEVAR first" in the emergency repair of ruptured thoracic aortic aneurysms, because the operative team often can intervene more quickly with an endovascular approach than with open surgical repair.

"I think there will be a lot of push to use the endovascular approach more frequently, because it is probably a lot quicker to set up your team," Dr. Gopaldas said. ""It’s quicker to get a TEVAR stent deployed than to cut open a patient’s chest. The endovascular team is probably geared to respond more quickly [than is] the open-heart surgical team in smaller hospitals. In bigger hospitals, there may not be as much of a difference."

The study used data collected by the Nationwide Inpatient Sample, an annual sampling of slightly more than 1,000 U.S. hospitals – about 20% of all U.S. patient discharge records – done by the Agency for Healthcare Research and Quality. Using data for 2006-2008, Dr. Gopaldas and his associates identified 923 patients who underwent emergency repair of a thoracic aortic aneurysm at one of 107 hospitals that performed these repairs. Among those hospitals, 41 (38%) performed TEVAR.

The analysis also divided hospitals into smaller and larger hospitals based on bed numbers. The definition of "smaller" differed based on U.S. geographical region (Northeast, Midwest, South, or West), rural vs. urban, and teaching vs. nonteaching hospitals. The bed sizes of smaller hospitals ranged from 1 to 449 (an urban teaching hospital in the Southern region). Larger hospitals included any center with a bed number larger than the study definition of smaller. Among the 107 hospitals that performed TEVAR during the study period, 27 (25%) were smaller hospitals.

In a risk-adjusted analysis, patients who underwent open surgical repair at a smaller hospital had a threefold increased risk for a subsequent complication, compared with patients treated by surgery at a larger hospital. But among the patients treated with TEVAR, the outcomes at smaller hospitals matched those that were achieved at larger hospitals. A comparison of open surgery and TEVAR outcomes within smaller hospitals showed that TEVAR led to a 79% lower complication rate, Dr. Gopaldas reported. In larger hospitals, outcomes were similar for patients treated with open surgery vs. TEVAR.

The risk-adjusted analysis also showed that once patients developed complications, they fared worse in smaller hospitals regardless of the type of aneurysm repair they received. Smaller hospitals had a failure-to-rescue rate that was nearly fourfold higher than that of larger hospitals. By lowering complication rates, TEVAR proved especially advantageous in smaller hospitals, Dr. Gopaldas said. He did these analyses in collaboration with researchers from Baylor College of Medicine and the Texas Heart Institute, also in Houston.

Dr. Gopaldas said that he had no relevant financial disclosures.

PHILADELPHIA – Endovascular repair may be better than open surgery for emergency treatment of patients with a thoracic aortic aneurysm rupture who receive care at smaller U.S. hospitals, based on an analysis of more than 900 patients treated during 2006-2008.

Investigators found that emergency thoracic endovascular aneurysm repair (TEVAR) led to a nearly 80% reduction in complications, compared with open surgical aneurysm repair, in patients who were treated at smaller U.S. hospitals. At larger hospitals, TEVAR and open repair produced similar outcomes, Dr. Raja R. Gopaldas said at the annual meeting of the American Association for Thoracic Surgery.

"TEVAR is an ideal alternative when transfer to a larger facility is not feasible," said Dr. Gopaldas, a cardiothoracic surgeon at the University of Missouri in Columbia.

"We were surprised when we saw that smaller hospitals had better outcomes with TEVAR, but it makes sense. A lot of hospitals lack expertise in open thoracic aortic repair because it requires a highly skilled surgeon, whereas a lot of small hospitals have a cardiac catheterization lab and a cardiologist or vascular surgeon available," he said in an interview. He added that open repair was more successful when performed at larger hospitals, but when TEVAR was used, results were similar.

Widespread availability of TEVAR catheter systems began in 2005. During 2006-2008, TEVAR was used in 40% of emergency thoracic aortic aneurysm repairs. Because these were the first 3 years after U.S. approval, such a high level of TEVAR use, especially in emergency circumstances, fell beyond Dr. Gopaldas’s expectations. "Forty percent is a huge number," he said.

The findings also suggested a role for "TEVAR first" in the emergency repair of ruptured thoracic aortic aneurysms, because the operative team often can intervene more quickly with an endovascular approach than with open surgical repair.

"I think there will be a lot of push to use the endovascular approach more frequently, because it is probably a lot quicker to set up your team," Dr. Gopaldas said. ""It’s quicker to get a TEVAR stent deployed than to cut open a patient’s chest. The endovascular team is probably geared to respond more quickly [than is] the open-heart surgical team in smaller hospitals. In bigger hospitals, there may not be as much of a difference."

The study used data collected by the Nationwide Inpatient Sample, an annual sampling of slightly more than 1,000 U.S. hospitals – about 20% of all U.S. patient discharge records – done by the Agency for Healthcare Research and Quality. Using data for 2006-2008, Dr. Gopaldas and his associates identified 923 patients who underwent emergency repair of a thoracic aortic aneurysm at one of 107 hospitals that performed these repairs. Among those hospitals, 41 (38%) performed TEVAR.

The analysis also divided hospitals into smaller and larger hospitals based on bed numbers. The definition of "smaller" differed based on U.S. geographical region (Northeast, Midwest, South, or West), rural vs. urban, and teaching vs. nonteaching hospitals. The bed sizes of smaller hospitals ranged from 1 to 449 (an urban teaching hospital in the Southern region). Larger hospitals included any center with a bed number larger than the study definition of smaller. Among the 107 hospitals that performed TEVAR during the study period, 27 (25%) were smaller hospitals.

In a risk-adjusted analysis, patients who underwent open surgical repair at a smaller hospital had a threefold increased risk for a subsequent complication, compared with patients treated by surgery at a larger hospital. But among the patients treated with TEVAR, the outcomes at smaller hospitals matched those that were achieved at larger hospitals. A comparison of open surgery and TEVAR outcomes within smaller hospitals showed that TEVAR led to a 79% lower complication rate, Dr. Gopaldas reported. In larger hospitals, outcomes were similar for patients treated with open surgery vs. TEVAR.

The risk-adjusted analysis also showed that once patients developed complications, they fared worse in smaller hospitals regardless of the type of aneurysm repair they received. Smaller hospitals had a failure-to-rescue rate that was nearly fourfold higher than that of larger hospitals. By lowering complication rates, TEVAR proved especially advantageous in smaller hospitals, Dr. Gopaldas said. He did these analyses in collaboration with researchers from Baylor College of Medicine and the Texas Heart Institute, also in Houston.

Dr. Gopaldas said that he had no relevant financial disclosures.

PHILADELPHIA – Endovascular repair may be better than open surgery for emergency treatment of patients with a thoracic aortic aneurysm rupture who receive care at smaller U.S. hospitals, based on an analysis of more than 900 patients treated during 2006-2008.

Investigators found that emergency thoracic endovascular aneurysm repair (TEVAR) led to a nearly 80% reduction in complications, compared with open surgical aneurysm repair, in patients who were treated at smaller U.S. hospitals. At larger hospitals, TEVAR and open repair produced similar outcomes, Dr. Raja R. Gopaldas said at the annual meeting of the American Association for Thoracic Surgery.

"TEVAR is an ideal alternative when transfer to a larger facility is not feasible," said Dr. Gopaldas, a cardiothoracic surgeon at the University of Missouri in Columbia.

"We were surprised when we saw that smaller hospitals had better outcomes with TEVAR, but it makes sense. A lot of hospitals lack expertise in open thoracic aortic repair because it requires a highly skilled surgeon, whereas a lot of small hospitals have a cardiac catheterization lab and a cardiologist or vascular surgeon available," he said in an interview. He added that open repair was more successful when performed at larger hospitals, but when TEVAR was used, results were similar.

Widespread availability of TEVAR catheter systems began in 2005. During 2006-2008, TEVAR was used in 40% of emergency thoracic aortic aneurysm repairs. Because these were the first 3 years after U.S. approval, such a high level of TEVAR use, especially in emergency circumstances, fell beyond Dr. Gopaldas’s expectations. "Forty percent is a huge number," he said.

The findings also suggested a role for "TEVAR first" in the emergency repair of ruptured thoracic aortic aneurysms, because the operative team often can intervene more quickly with an endovascular approach than with open surgical repair.

"I think there will be a lot of push to use the endovascular approach more frequently, because it is probably a lot quicker to set up your team," Dr. Gopaldas said. ""It’s quicker to get a TEVAR stent deployed than to cut open a patient’s chest. The endovascular team is probably geared to respond more quickly [than is] the open-heart surgical team in smaller hospitals. In bigger hospitals, there may not be as much of a difference."

The study used data collected by the Nationwide Inpatient Sample, an annual sampling of slightly more than 1,000 U.S. hospitals – about 20% of all U.S. patient discharge records – done by the Agency for Healthcare Research and Quality. Using data for 2006-2008, Dr. Gopaldas and his associates identified 923 patients who underwent emergency repair of a thoracic aortic aneurysm at one of 107 hospitals that performed these repairs. Among those hospitals, 41 (38%) performed TEVAR.

The analysis also divided hospitals into smaller and larger hospitals based on bed numbers. The definition of "smaller" differed based on U.S. geographical region (Northeast, Midwest, South, or West), rural vs. urban, and teaching vs. nonteaching hospitals. The bed sizes of smaller hospitals ranged from 1 to 449 (an urban teaching hospital in the Southern region). Larger hospitals included any center with a bed number larger than the study definition of smaller. Among the 107 hospitals that performed TEVAR during the study period, 27 (25%) were smaller hospitals.

In a risk-adjusted analysis, patients who underwent open surgical repair at a smaller hospital had a threefold increased risk for a subsequent complication, compared with patients treated by surgery at a larger hospital. But among the patients treated with TEVAR, the outcomes at smaller hospitals matched those that were achieved at larger hospitals. A comparison of open surgery and TEVAR outcomes within smaller hospitals showed that TEVAR led to a 79% lower complication rate, Dr. Gopaldas reported. In larger hospitals, outcomes were similar for patients treated with open surgery vs. TEVAR.

The risk-adjusted analysis also showed that once patients developed complications, they fared worse in smaller hospitals regardless of the type of aneurysm repair they received. Smaller hospitals had a failure-to-rescue rate that was nearly fourfold higher than that of larger hospitals. By lowering complication rates, TEVAR proved especially advantageous in smaller hospitals, Dr. Gopaldas said. He did these analyses in collaboration with researchers from Baylor College of Medicine and the Texas Heart Institute, also in Houston.

Dr. Gopaldas said that he had no relevant financial disclosures.

LONDON – A single 5-mg infusion of zoledronic acid, a bisphosphonate, in patients with knee osteoarthritis led to significant pain reduction and shrinkage of bone marrow lesions in a randomized, placebo-controlled study with 59 patients.

The zoledronic acid treatment led to an average 15-point drop in pain (on a visual analog scale of 0-100) beyond what occurred in the placebo group, and the active treatment was also linked with an average 170-mm² reduction in maximal bone marrow lesion (BML) area beyond the placebo-treated patients, which was a cut in BML area of about 37%, compared with the starting BML area, Dr. Graeme Jones said at the annual European Congress of Rheumatology. Dr. Jones visualizes BMLs using MRI knee scans.

"This is the first intervention shown to work on BMLs" in patients with osteoarthritis (OA), said Dr. Jones, professor of rheumatology and epidemiology and head of the musculoskeletal unit at the Menzies Research Institute Tasmania, Hobart, Australia.

"This is exciting for treating existing OA. It is one of the first positive structure modification trials," commented Dr. Philip Conaghan, professor and chairman of musculoskeletal medicine at the University of Leeds (England).

"Results from several studies have linked BMLs with pain and cartilage damage in OA patients. The larger the BML, the faster the cartilage loss and the worse the pain," Dr. Jones said in an interview. Based on studies his group has done, about 20% of BMLs that are associated with knee OA spontaneously enlarge over the course of 3 years, another 20% shrink in size, and about 60% remain the same, he said. Their earlier research findings also showed that BMLs are independently linked with fast progression of OA and the need for knee replacement. "If you reduce BMLs, it should produce good outcomes in patients," he said.

"The next step is to show that treatment with zoledronic acid not only reduces BML size but also slows cartilage loss. Sixty patients followed for 12 months were not enough to assess cartilage. We will need about 400 patients followed for 2 years," Dr. Jones added.

Despite not yet having information on cartilage effects, he said that his results so far have convinced him that treatment with zoledronic acid is reasonable for patients with painful knee OA and BMLs.

"I use it off label. Patients need to know it’s off label, and they [therefore] must be willing to pay for it, but I use it. It’s been shown to work, and nothing else works. Zoledronic acid [Reclast] is available, we know about its safety, and it’s been used for a long time to treat osteoporosis and cancers. If you have OA patients with BMLs, this is something to actively consider for them. Patients with OA have very limited treatment options. This can make a large difference in their pain, and it has long-lasting benefit so it can be given once a year," Dr. Jones said.

He recommended an infusion of 5 mg of zoledronic acid for patients who are at least 50 years old with knee OA that fulfills the American College of Rheumatology clinical criteria, and knee BMLs that are visible on an MRI scan of the affected knee. In his experience, 88% of these knee OA patients have BMLs. Dr. Jones noted that he does not use a maximal BML area threshold for initiating treatment, although in his study the average maximal BML area was about 465 mm². About one-third of people aged 50 years or older with no clinical evidence of OA also have BMLs, he noted.

The benefits of zoledronic acid that were seen in his study might be a class effect that may be replicated by treatment with another bisphosphonate, but zoledronic acid is more potent than oral bisphosphonates and hence the drug’s beneficial effect on pain and BML shrinkage may exceed the effect that other bisphosphonates might have, he said.

The pain benefit appeared to start wearing off about a year after the zoledronic acid injection. Dr. Jones said that he has a small number of patients whom he has infused a second time, which produced a second round of pain reduction. He has not yet given any OA patients a third dose of the drug.

The 59 patients who were enrolled in the study had an average age of about 60 years, with an average knee pain score of about 52 on the visual analog scale; all patients had BMLs as seen on MRI scans of their affected knees. In all, 31 patients received a 5-mg infusion of zoledronic acid and 28 patients received a placebo infusion. All patients also continued their conventional pain medication regimens. The zoledronic acid infusion was well tolerated: Although infusion reactions were reported in 90% of the patients who received the drug and in 43% of the placebo patients, serious adverse effects occurred in only 19% of the patients who received zoledronic acid and in 4% of the placebo patients.

The Food and Drug Administration has approved zoledronic acid under a number of brand names to prevent or treat osteoporosis in postmenopausal women or patients who are at risk for osteoporosis because they are taking or have taken corticosteroid therapy; to manage Paget disease; and to prevent chemotherapy-induced bone fractures or fractures in patients with multiple myeloma or cancer that has metastasized to the bones from other locations.

The study was funded by Novartis, which markets zoledronic acid (Reclast). Dr. Jones and Dr. Conaghan said that they had no disclosures.

*Correction, 6/6/2011: An earlier version of this story incorrectly stated that Dr. Jones had no disclosures. Dr. Jones has received speaker fees, travel sponsorship, and research support from Novartis and from several other drug companies.

LONDON – A single 5-mg infusion of zoledronic acid, a bisphosphonate, in patients with knee osteoarthritis led to significant pain reduction and shrinkage of bone marrow lesions in a randomized, placebo-controlled study with 59 patients.

The zoledronic acid treatment led to an average 15-point drop in pain (on a visual analog scale of 0-100) beyond what occurred in the placebo group, and the active treatment was also linked with an average 170-mm² reduction in maximal bone marrow lesion (BML) area beyond the placebo-treated patients, which was a cut in BML area of about 37%, compared with the starting BML area, Dr. Graeme Jones said at the annual European Congress of Rheumatology. Dr. Jones visualizes BMLs using MRI knee scans.

"This is the first intervention shown to work on BMLs" in patients with osteoarthritis (OA), said Dr. Jones, professor of rheumatology and epidemiology and head of the musculoskeletal unit at the Menzies Research Institute Tasmania, Hobart, Australia.

"This is exciting for treating existing OA. It is one of the first positive structure modification trials," commented Dr. Philip Conaghan, professor and chairman of musculoskeletal medicine at the University of Leeds (England).

"Results from several studies have linked BMLs with pain and cartilage damage in OA patients. The larger the BML, the faster the cartilage loss and the worse the pain," Dr. Jones said in an interview. Based on studies his group has done, about 20% of BMLs that are associated with knee OA spontaneously enlarge over the course of 3 years, another 20% shrink in size, and about 60% remain the same, he said. Their earlier research findings also showed that BMLs are independently linked with fast progression of OA and the need for knee replacement. "If you reduce BMLs, it should produce good outcomes in patients," he said.

"The next step is to show that treatment with zoledronic acid not only reduces BML size but also slows cartilage loss. Sixty patients followed for 12 months were not enough to assess cartilage. We will need about 400 patients followed for 2 years," Dr. Jones added.

Despite not yet having information on cartilage effects, he said that his results so far have convinced him that treatment with zoledronic acid is reasonable for patients with painful knee OA and BMLs.

"I use it off label. Patients need to know it’s off label, and they [therefore] must be willing to pay for it, but I use it. It’s been shown to work, and nothing else works. Zoledronic acid [Reclast] is available, we know about its safety, and it’s been used for a long time to treat osteoporosis and cancers. If you have OA patients with BMLs, this is something to actively consider for them. Patients with OA have very limited treatment options. This can make a large difference in their pain, and it has long-lasting benefit so it can be given once a year," Dr. Jones said.

He recommended an infusion of 5 mg of zoledronic acid for patients who are at least 50 years old with knee OA that fulfills the American College of Rheumatology clinical criteria, and knee BMLs that are visible on an MRI scan of the affected knee. In his experience, 88% of these knee OA patients have BMLs. Dr. Jones noted that he does not use a maximal BML area threshold for initiating treatment, although in his study the average maximal BML area was about 465 mm². About one-third of people aged 50 years or older with no clinical evidence of OA also have BMLs, he noted.

The benefits of zoledronic acid that were seen in his study might be a class effect that may be replicated by treatment with another bisphosphonate, but zoledronic acid is more potent than oral bisphosphonates and hence the drug’s beneficial effect on pain and BML shrinkage may exceed the effect that other bisphosphonates might have, he said.

The pain benefit appeared to start wearing off about a year after the zoledronic acid injection. Dr. Jones said that he has a small number of patients whom he has infused a second time, which produced a second round of pain reduction. He has not yet given any OA patients a third dose of the drug.

The 59 patients who were enrolled in the study had an average age of about 60 years, with an average knee pain score of about 52 on the visual analog scale; all patients had BMLs as seen on MRI scans of their affected knees. In all, 31 patients received a 5-mg infusion of zoledronic acid and 28 patients received a placebo infusion. All patients also continued their conventional pain medication regimens. The zoledronic acid infusion was well tolerated: Although infusion reactions were reported in 90% of the patients who received the drug and in 43% of the placebo patients, serious adverse effects occurred in only 19% of the patients who received zoledronic acid and in 4% of the placebo patients.

The Food and Drug Administration has approved zoledronic acid under a number of brand names to prevent or treat osteoporosis in postmenopausal women or patients who are at risk for osteoporosis because they are taking or have taken corticosteroid therapy; to manage Paget disease; and to prevent chemotherapy-induced bone fractures or fractures in patients with multiple myeloma or cancer that has metastasized to the bones from other locations.

The study was funded by Novartis, which markets zoledronic acid (Reclast). Dr. Jones and Dr. Conaghan said that they had no disclosures.

*Correction, 6/6/2011: An earlier version of this story incorrectly stated that Dr. Jones had no disclosures. Dr. Jones has received speaker fees, travel sponsorship, and research support from Novartis and from several other drug companies.

LONDON – A single 5-mg infusion of zoledronic acid, a bisphosphonate, in patients with knee osteoarthritis led to significant pain reduction and shrinkage of bone marrow lesions in a randomized, placebo-controlled study with 59 patients.

The zoledronic acid treatment led to an average 15-point drop in pain (on a visual analog scale of 0-100) beyond what occurred in the placebo group, and the active treatment was also linked with an average 170-mm² reduction in maximal bone marrow lesion (BML) area beyond the placebo-treated patients, which was a cut in BML area of about 37%, compared with the starting BML area, Dr. Graeme Jones said at the annual European Congress of Rheumatology. Dr. Jones visualizes BMLs using MRI knee scans.

"This is the first intervention shown to work on BMLs" in patients with osteoarthritis (OA), said Dr. Jones, professor of rheumatology and epidemiology and head of the musculoskeletal unit at the Menzies Research Institute Tasmania, Hobart, Australia.

"This is exciting for treating existing OA. It is one of the first positive structure modification trials," commented Dr. Philip Conaghan, professor and chairman of musculoskeletal medicine at the University of Leeds (England).

"Results from several studies have linked BMLs with pain and cartilage damage in OA patients. The larger the BML, the faster the cartilage loss and the worse the pain," Dr. Jones said in an interview. Based on studies his group has done, about 20% of BMLs that are associated with knee OA spontaneously enlarge over the course of 3 years, another 20% shrink in size, and about 60% remain the same, he said. Their earlier research findings also showed that BMLs are independently linked with fast progression of OA and the need for knee replacement. "If you reduce BMLs, it should produce good outcomes in patients," he said.

"The next step is to show that treatment with zoledronic acid not only reduces BML size but also slows cartilage loss. Sixty patients followed for 12 months were not enough to assess cartilage. We will need about 400 patients followed for 2 years," Dr. Jones added.

Despite not yet having information on cartilage effects, he said that his results so far have convinced him that treatment with zoledronic acid is reasonable for patients with painful knee OA and BMLs.

"I use it off label. Patients need to know it’s off label, and they [therefore] must be willing to pay for it, but I use it. It’s been shown to work, and nothing else works. Zoledronic acid [Reclast] is available, we know about its safety, and it’s been used for a long time to treat osteoporosis and cancers. If you have OA patients with BMLs, this is something to actively consider for them. Patients with OA have very limited treatment options. This can make a large difference in their pain, and it has long-lasting benefit so it can be given once a year," Dr. Jones said.

He recommended an infusion of 5 mg of zoledronic acid for patients who are at least 50 years old with knee OA that fulfills the American College of Rheumatology clinical criteria, and knee BMLs that are visible on an MRI scan of the affected knee. In his experience, 88% of these knee OA patients have BMLs. Dr. Jones noted that he does not use a maximal BML area threshold for initiating treatment, although in his study the average maximal BML area was about 465 mm². About one-third of people aged 50 years or older with no clinical evidence of OA also have BMLs, he noted.

The benefits of zoledronic acid that were seen in his study might be a class effect that may be replicated by treatment with another bisphosphonate, but zoledronic acid is more potent than oral bisphosphonates and hence the drug’s beneficial effect on pain and BML shrinkage may exceed the effect that other bisphosphonates might have, he said.

The pain benefit appeared to start wearing off about a year after the zoledronic acid injection. Dr. Jones said that he has a small number of patients whom he has infused a second time, which produced a second round of pain reduction. He has not yet given any OA patients a third dose of the drug.

The 59 patients who were enrolled in the study had an average age of about 60 years, with an average knee pain score of about 52 on the visual analog scale; all patients had BMLs as seen on MRI scans of their affected knees. In all, 31 patients received a 5-mg infusion of zoledronic acid and 28 patients received a placebo infusion. All patients also continued their conventional pain medication regimens. The zoledronic acid infusion was well tolerated: Although infusion reactions were reported in 90% of the patients who received the drug and in 43% of the placebo patients, serious adverse effects occurred in only 19% of the patients who received zoledronic acid and in 4% of the placebo patients.

The Food and Drug Administration has approved zoledronic acid under a number of brand names to prevent or treat osteoporosis in postmenopausal women or patients who are at risk for osteoporosis because they are taking or have taken corticosteroid therapy; to manage Paget disease; and to prevent chemotherapy-induced bone fractures or fractures in patients with multiple myeloma or cancer that has metastasized to the bones from other locations.

The study was funded by Novartis, which markets zoledronic acid (Reclast). Dr. Jones and Dr. Conaghan said that they had no disclosures.

*Correction, 6/6/2011: An earlier version of this story incorrectly stated that Dr. Jones had no disclosures. Dr. Jones has received speaker fees, travel sponsorship, and research support from Novartis and from several other drug companies.