ATLANTA—Due to results of the AMPLIFY-EXTENSION study, researchers are recommending a new indication for apixaban: long-term use to prevent recurrent venous thromboembolism (VTE).

Study investigators compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.

The team found that both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.

“We believe that the study, given the results we achieved, should support the use of apixaban for the extended treatment of VTE,” said Giancarlo Agnelli, MD, of the University of Perugia in Italy. 

Dr Agnelli presented these results in the late-breaking abstract session (LBA-1) of the 54th ASH Annual Meeting, which took place here December 8-11.

More detailed results of the study—which was funded by Bristol-Myers Squibb and Pfizer, joint developers of apixaban—have been published in NEJM.

Dr Agnelli noted that apixaban has proven effective as VTE prophylaxis when given at 2.5 mg after hip or knee replacement surgery. And the drug has been administered at 5 mg as stroke prevention in patients with atrial fibrillation.

So he and his colleagues wanted to determine if apixaban might be effective as long-term VTE prophylaxis in patients with a previous thrombotic event, as well as which dose might be optimal for these patients.

To find out, the researchers enrolled 2482 patients with a prior VTE who had completed 6 to 12 months of oral anticoagulant treatment without VTE recurrence or bleeding.

The team randomized 840 patients to receive apixaban at 2.5 mg BID, 813 patients to receive the drug at 5 mg BID, and 829 patients to receive placebo.

The patients were well-matched according age, gender, weight, initial diagnosis, and VTE clinical presentation. They received treatment for 12 months, after which they were followed for 30 days.

Efficacy data

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The researchers also calculated the incidence of recurrent VTE or VTE-related death. And these events occurred in 14 patients (1.7%) in the 2.5-mg arm, 14 patients (1.7%) in the 5-mg arm, and 73 patients (8.8%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

A third composite endpoint consisted of recurrent VTE, VTE-related death, myocardial infarction, stroke, or cardiovascular-related death. This endpoint was met by 18 patients (2.1%) in the 2.5-mg arm, 19 patients (2.3%) in the 5-mg arm, and 83 patients (10.0%) in the placebo arm.

Overall, both doses of apixaban reduced the risk of fatal and non-fatal recurrent venous thromboembolism by 80%, Dr Agnelli said.

Events during follow-up

During the 30-day follow-up period, symptomatic, recurrent VTE occurred in 2 patients (0.2%) who had received placebo, 3 patients (0.4%) who had received apixaban at 2.5 mg, and 5 patients (0.6%) who had received apixaban at 5 mg.

The composite outcome of myocardial infarction, stroke, or death related to cardiovascular disease occurred in 2 patients: 1 who had received the lower dose of apixaban and 1 who received the higher dose.

Safety data

The study’s primary safety endpoint was major bleeding. In the 2.5-mg arm, 2 patients (0.2%) experienced major bleeding events, both of which were intraocular bleeds.

One patient (0.1%) in the 5-mg arm experienced a major gastrointestinal bleed. And 4 patients (0.5%) in the placebo arm experienced major bleeding events, including 1 intraocular bleed, 1 stroke, 1 urogenital bleed, and 1 gastrointestinal bleed.

A secondary endpoint was clinically relevant, non-major bleeding. This occurred in 25 patients (3.0%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 19 patients (2.3%) in the placebo arm.

Dr Agnelli and his colleagues also combined the major bleeding data and the clinically relevant, non-major bleeding data. So 27 patients (3.2%) in the 2.5-mg arm had a bleeding event of either kind, as did 35 patients (4.3%) in the 5-mg arm and 22 patients (2.7%) in the placebo arm.

Clinical interpretation

Finally, the researchers tried to put this data into a clinical context. They calculated the number of patients needed to treat 1 recurrent VTE in each of the apixaban arms. And they found that number was 14 patients per year with both doses of the drug.

The team also calculated the number of patients needed to inflict harm, in the form of 1 major or clinically relevant, non-major bleeding event. And they found that number was 200 patients per year in the 2.5-mg arm and 63 patients per year in the 5-mg arm.  

In closing, Dr Agnelli said these results support the use of apixaban as long-term thromboprophylaxis in patients with a prior VTE.

“And, as a matter of speculation, we do believe that, given the similar efficacy and the possibility of less clinically relevant non-major bleeding, the dose of 2.5 mg of apixaban would be preferred by the clinician,” he added.

ATLANTA—Due to results of the AMPLIFY-EXTENSION study, researchers are recommending a new indication for apixaban: long-term use to prevent recurrent venous thromboembolism (VTE).

Study investigators compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.

The team found that both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.

“We believe that the study, given the results we achieved, should support the use of apixaban for the extended treatment of VTE,” said Giancarlo Agnelli, MD, of the University of Perugia in Italy. 

Dr Agnelli presented these results in the late-breaking abstract session (LBA-1) of the 54th ASH Annual Meeting, which took place here December 8-11.

More detailed results of the study—which was funded by Bristol-Myers Squibb and Pfizer, joint developers of apixaban—have been published in NEJM.

Dr Agnelli noted that apixaban has proven effective as VTE prophylaxis when given at 2.5 mg after hip or knee replacement surgery. And the drug has been administered at 5 mg as stroke prevention in patients with atrial fibrillation.

So he and his colleagues wanted to determine if apixaban might be effective as long-term VTE prophylaxis in patients with a previous thrombotic event, as well as which dose might be optimal for these patients.

To find out, the researchers enrolled 2482 patients with a prior VTE who had completed 6 to 12 months of oral anticoagulant treatment without VTE recurrence or bleeding.

The team randomized 840 patients to receive apixaban at 2.5 mg BID, 813 patients to receive the drug at 5 mg BID, and 829 patients to receive placebo.

The patients were well-matched according age, gender, weight, initial diagnosis, and VTE clinical presentation. They received treatment for 12 months, after which they were followed for 30 days.

Efficacy data

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The researchers also calculated the incidence of recurrent VTE or VTE-related death. And these events occurred in 14 patients (1.7%) in the 2.5-mg arm, 14 patients (1.7%) in the 5-mg arm, and 73 patients (8.8%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

A third composite endpoint consisted of recurrent VTE, VTE-related death, myocardial infarction, stroke, or cardiovascular-related death. This endpoint was met by 18 patients (2.1%) in the 2.5-mg arm, 19 patients (2.3%) in the 5-mg arm, and 83 patients (10.0%) in the placebo arm.

Overall, both doses of apixaban reduced the risk of fatal and non-fatal recurrent venous thromboembolism by 80%, Dr Agnelli said.

Events during follow-up

During the 30-day follow-up period, symptomatic, recurrent VTE occurred in 2 patients (0.2%) who had received placebo, 3 patients (0.4%) who had received apixaban at 2.5 mg, and 5 patients (0.6%) who had received apixaban at 5 mg.

The composite outcome of myocardial infarction, stroke, or death related to cardiovascular disease occurred in 2 patients: 1 who had received the lower dose of apixaban and 1 who received the higher dose.

Safety data

The study’s primary safety endpoint was major bleeding. In the 2.5-mg arm, 2 patients (0.2%) experienced major bleeding events, both of which were intraocular bleeds.

One patient (0.1%) in the 5-mg arm experienced a major gastrointestinal bleed. And 4 patients (0.5%) in the placebo arm experienced major bleeding events, including 1 intraocular bleed, 1 stroke, 1 urogenital bleed, and 1 gastrointestinal bleed.

A secondary endpoint was clinically relevant, non-major bleeding. This occurred in 25 patients (3.0%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 19 patients (2.3%) in the placebo arm.

Dr Agnelli and his colleagues also combined the major bleeding data and the clinically relevant, non-major bleeding data. So 27 patients (3.2%) in the 2.5-mg arm had a bleeding event of either kind, as did 35 patients (4.3%) in the 5-mg arm and 22 patients (2.7%) in the placebo arm.

Clinical interpretation

Finally, the researchers tried to put this data into a clinical context. They calculated the number of patients needed to treat 1 recurrent VTE in each of the apixaban arms. And they found that number was 14 patients per year with both doses of the drug.

The team also calculated the number of patients needed to inflict harm, in the form of 1 major or clinically relevant, non-major bleeding event. And they found that number was 200 patients per year in the 2.5-mg arm and 63 patients per year in the 5-mg arm.  

In closing, Dr Agnelli said these results support the use of apixaban as long-term thromboprophylaxis in patients with a prior VTE.

“And, as a matter of speculation, we do believe that, given the similar efficacy and the possibility of less clinically relevant non-major bleeding, the dose of 2.5 mg of apixaban would be preferred by the clinician,” he added.

ATLANTA—Due to results of the AMPLIFY-EXTENSION study, researchers are recommending a new indication for apixaban: long-term use to prevent recurrent venous thromboembolism (VTE).

Study investigators compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.

The team found that both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.

“We believe that the study, given the results we achieved, should support the use of apixaban for the extended treatment of VTE,” said Giancarlo Agnelli, MD, of the University of Perugia in Italy. 

Dr Agnelli presented these results in the late-breaking abstract session (LBA-1) of the 54th ASH Annual Meeting, which took place here December 8-11.

More detailed results of the study—which was funded by Bristol-Myers Squibb and Pfizer, joint developers of apixaban—have been published in NEJM.

Dr Agnelli noted that apixaban has proven effective as VTE prophylaxis when given at 2.5 mg after hip or knee replacement surgery. And the drug has been administered at 5 mg as stroke prevention in patients with atrial fibrillation.

So he and his colleagues wanted to determine if apixaban might be effective as long-term VTE prophylaxis in patients with a previous thrombotic event, as well as which dose might be optimal for these patients.

To find out, the researchers enrolled 2482 patients with a prior VTE who had completed 6 to 12 months of oral anticoagulant treatment without VTE recurrence or bleeding.

The team randomized 840 patients to receive apixaban at 2.5 mg BID, 813 patients to receive the drug at 5 mg BID, and 829 patients to receive placebo.

The patients were well-matched according age, gender, weight, initial diagnosis, and VTE clinical presentation. They received treatment for 12 months, after which they were followed for 30 days.

Efficacy data

The study’s primary efficacy endpoint was recurrent VTE or all-cause death. During the 12-month active study period, these events occurred in 32 patients (3.8%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 96 patients (11.6%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

The researchers also calculated the incidence of recurrent VTE or VTE-related death. And these events occurred in 14 patients (1.7%) in the 2.5-mg arm, 14 patients (1.7%) in the 5-mg arm, and 73 patients (8.8%) in the placebo arm. Both apixaban doses were significantly superior to placebo (P<0.001).

A third composite endpoint consisted of recurrent VTE, VTE-related death, myocardial infarction, stroke, or cardiovascular-related death. This endpoint was met by 18 patients (2.1%) in the 2.5-mg arm, 19 patients (2.3%) in the 5-mg arm, and 83 patients (10.0%) in the placebo arm.

Overall, both doses of apixaban reduced the risk of fatal and non-fatal recurrent venous thromboembolism by 80%, Dr Agnelli said.

Events during follow-up

During the 30-day follow-up period, symptomatic, recurrent VTE occurred in 2 patients (0.2%) who had received placebo, 3 patients (0.4%) who had received apixaban at 2.5 mg, and 5 patients (0.6%) who had received apixaban at 5 mg.

The composite outcome of myocardial infarction, stroke, or death related to cardiovascular disease occurred in 2 patients: 1 who had received the lower dose of apixaban and 1 who received the higher dose.

Safety data

The study’s primary safety endpoint was major bleeding. In the 2.5-mg arm, 2 patients (0.2%) experienced major bleeding events, both of which were intraocular bleeds.

One patient (0.1%) in the 5-mg arm experienced a major gastrointestinal bleed. And 4 patients (0.5%) in the placebo arm experienced major bleeding events, including 1 intraocular bleed, 1 stroke, 1 urogenital bleed, and 1 gastrointestinal bleed.

A secondary endpoint was clinically relevant, non-major bleeding. This occurred in 25 patients (3.0%) in the 2.5-mg arm, 34 patients (4.2%) in the 5-mg arm, and 19 patients (2.3%) in the placebo arm.

Dr Agnelli and his colleagues also combined the major bleeding data and the clinically relevant, non-major bleeding data. So 27 patients (3.2%) in the 2.5-mg arm had a bleeding event of either kind, as did 35 patients (4.3%) in the 5-mg arm and 22 patients (2.7%) in the placebo arm.

Clinical interpretation

Finally, the researchers tried to put this data into a clinical context. They calculated the number of patients needed to treat 1 recurrent VTE in each of the apixaban arms. And they found that number was 14 patients per year with both doses of the drug.

The team also calculated the number of patients needed to inflict harm, in the form of 1 major or clinically relevant, non-major bleeding event. And they found that number was 200 patients per year in the 2.5-mg arm and 63 patients per year in the 5-mg arm.  

In closing, Dr Agnelli said these results support the use of apixaban as long-term thromboprophylaxis in patients with a prior VTE.

“And, as a matter of speculation, we do believe that, given the similar efficacy and the possibility of less clinically relevant non-major bleeding, the dose of 2.5 mg of apixaban would be preferred by the clinician,” he added.

BOSTON – Adding pegylated interferon alfa-2a to entecavir increased the likelihood of long-term viral suppression of chronic hepatitis B infections in a randomized trial of 160 patients with chronic hepatitis B virus infections.

Loss of the hepatitis B e antigen (HBeAg) and hepatitis B viral (HBV) DNA levels below 200 IU/mL after 48 weeks of therapy occurred in 18% of patients who were randomized to entecavir (Baraclude) and pegylated interferon alfa-2a (Pegasys), compared with 8% of patients on entecavir monotherapy, but this difference was not significant, Dr. Milan J. Sonneveld reported at the annual meeting of the American Association for the Study of Liver Diseases.

However, after adjustment for baseline HBV serum antigen levels, analysis showed that pegylated interferon alfa-2a (PEG IFN) as an add-on was independently associated with response at 48 weeks (P = .01).

"Adding peginterferon alfa-2a to a potent nucleoside analogue appears to be a possibility to increase the probability of finite treatment in e-antigen–positive chronic hepatitis B patients," said Dr. Sonneveld of the department of gastroenterology and hepatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Investigators at 15 sites in Europe and China enrolled 184 patients with HBeAg-positive infections with compensated liver disease. The patients were randomized to either entecavir alone at a dose of 0.5 mg daily for 48 weeks, or 24 weeks of entecavir monotherapy, after which 24 weeks of PEG IFN alfa-2a 180 mcg weekly were added.

All patients were assessed at weeks 12, 24, 36, and 48. Those with a response – a loss of the HBeAg with HBV DNA less than 200 IU/mL at 48 weeks – received an additional 24 weeks of consolidation therapy with entecavir and then discontinued therapy, whereas those without a response were continued on entecavir through week 72.

At week 48, there were 77 patients assigned to entecavir and PEG IFN and 83 assigned to entecavir alone.

There were no significant differences in response rates between the treatment arms, but patients who received the PEG IFN add-on had a greater decline of HBV DNA (6.33 vs. 5.91 log IU/mL; P = .05), HBeAg (1.99 vs. 1.56 log IU/mL; P = .01) and HBV serum antigen (0.84 vs. 0.32 log IU/mL; P less than .001) at week 48.

HBV serum antigen clearance was seen in only one patient at week 48; he had been assigned to the PEG IFN add-on group.

In a multivariate analysis adjusted for differences in baseline serum antigen levels, the addition of PEG IFN was independently associated with response at week 48 (adjusted odds ratio, 3.78; P = .012).

There were no differences in anemia between the two groups, but patients on the entecavir plus PEG IFN combination had significantly more leukopenia (8% vs. 0%; P = .01), neutropenia (23% vs. 0%; P = .001), and thrombocytopenia (P = .01).

The study was supported by Bristol-Myers Squibb, which manufactures entecavir, and Roche, which manufactures pegylated interferon alfa-2a. Dr. Sonneveld reported receiving speakers fees and educational support from Roche.

BOSTON – Adding pegylated interferon alfa-2a to entecavir increased the likelihood of long-term viral suppression of chronic hepatitis B infections in a randomized trial of 160 patients with chronic hepatitis B virus infections.

Loss of the hepatitis B e antigen (HBeAg) and hepatitis B viral (HBV) DNA levels below 200 IU/mL after 48 weeks of therapy occurred in 18% of patients who were randomized to entecavir (Baraclude) and pegylated interferon alfa-2a (Pegasys), compared with 8% of patients on entecavir monotherapy, but this difference was not significant, Dr. Milan J. Sonneveld reported at the annual meeting of the American Association for the Study of Liver Diseases.

However, after adjustment for baseline HBV serum antigen levels, analysis showed that pegylated interferon alfa-2a (PEG IFN) as an add-on was independently associated with response at 48 weeks (P = .01).

"Adding peginterferon alfa-2a to a potent nucleoside analogue appears to be a possibility to increase the probability of finite treatment in e-antigen–positive chronic hepatitis B patients," said Dr. Sonneveld of the department of gastroenterology and hepatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Investigators at 15 sites in Europe and China enrolled 184 patients with HBeAg-positive infections with compensated liver disease. The patients were randomized to either entecavir alone at a dose of 0.5 mg daily for 48 weeks, or 24 weeks of entecavir monotherapy, after which 24 weeks of PEG IFN alfa-2a 180 mcg weekly were added.

All patients were assessed at weeks 12, 24, 36, and 48. Those with a response – a loss of the HBeAg with HBV DNA less than 200 IU/mL at 48 weeks – received an additional 24 weeks of consolidation therapy with entecavir and then discontinued therapy, whereas those without a response were continued on entecavir through week 72.

At week 48, there were 77 patients assigned to entecavir and PEG IFN and 83 assigned to entecavir alone.

There were no significant differences in response rates between the treatment arms, but patients who received the PEG IFN add-on had a greater decline of HBV DNA (6.33 vs. 5.91 log IU/mL; P = .05), HBeAg (1.99 vs. 1.56 log IU/mL; P = .01) and HBV serum antigen (0.84 vs. 0.32 log IU/mL; P less than .001) at week 48.

HBV serum antigen clearance was seen in only one patient at week 48; he had been assigned to the PEG IFN add-on group.

In a multivariate analysis adjusted for differences in baseline serum antigen levels, the addition of PEG IFN was independently associated with response at week 48 (adjusted odds ratio, 3.78; P = .012).

There were no differences in anemia between the two groups, but patients on the entecavir plus PEG IFN combination had significantly more leukopenia (8% vs. 0%; P = .01), neutropenia (23% vs. 0%; P = .001), and thrombocytopenia (P = .01).

The study was supported by Bristol-Myers Squibb, which manufactures entecavir, and Roche, which manufactures pegylated interferon alfa-2a. Dr. Sonneveld reported receiving speakers fees and educational support from Roche.

BOSTON – Adding pegylated interferon alfa-2a to entecavir increased the likelihood of long-term viral suppression of chronic hepatitis B infections in a randomized trial of 160 patients with chronic hepatitis B virus infections.

Loss of the hepatitis B e antigen (HBeAg) and hepatitis B viral (HBV) DNA levels below 200 IU/mL after 48 weeks of therapy occurred in 18% of patients who were randomized to entecavir (Baraclude) and pegylated interferon alfa-2a (Pegasys), compared with 8% of patients on entecavir monotherapy, but this difference was not significant, Dr. Milan J. Sonneveld reported at the annual meeting of the American Association for the Study of Liver Diseases.

However, after adjustment for baseline HBV serum antigen levels, analysis showed that pegylated interferon alfa-2a (PEG IFN) as an add-on was independently associated with response at 48 weeks (P = .01).

"Adding peginterferon alfa-2a to a potent nucleoside analogue appears to be a possibility to increase the probability of finite treatment in e-antigen–positive chronic hepatitis B patients," said Dr. Sonneveld of the department of gastroenterology and hepatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Investigators at 15 sites in Europe and China enrolled 184 patients with HBeAg-positive infections with compensated liver disease. The patients were randomized to either entecavir alone at a dose of 0.5 mg daily for 48 weeks, or 24 weeks of entecavir monotherapy, after which 24 weeks of PEG IFN alfa-2a 180 mcg weekly were added.

All patients were assessed at weeks 12, 24, 36, and 48. Those with a response – a loss of the HBeAg with HBV DNA less than 200 IU/mL at 48 weeks – received an additional 24 weeks of consolidation therapy with entecavir and then discontinued therapy, whereas those without a response were continued on entecavir through week 72.

At week 48, there were 77 patients assigned to entecavir and PEG IFN and 83 assigned to entecavir alone.

There were no significant differences in response rates between the treatment arms, but patients who received the PEG IFN add-on had a greater decline of HBV DNA (6.33 vs. 5.91 log IU/mL; P = .05), HBeAg (1.99 vs. 1.56 log IU/mL; P = .01) and HBV serum antigen (0.84 vs. 0.32 log IU/mL; P less than .001) at week 48.

HBV serum antigen clearance was seen in only one patient at week 48; he had been assigned to the PEG IFN add-on group.

In a multivariate analysis adjusted for differences in baseline serum antigen levels, the addition of PEG IFN was independently associated with response at week 48 (adjusted odds ratio, 3.78; P = .012).

There were no differences in anemia between the two groups, but patients on the entecavir plus PEG IFN combination had significantly more leukopenia (8% vs. 0%; P = .01), neutropenia (23% vs. 0%; P = .001), and thrombocytopenia (P = .01).

The study was supported by Bristol-Myers Squibb, which manufactures entecavir, and Roche, which manufactures pegylated interferon alfa-2a. Dr. Sonneveld reported receiving speakers fees and educational support from Roche.

Need another reason to hone your skills in treating people with kidney disease?

Take a look at a study out of the University of Washington: Kidney disease, researchers there found, is the diagnosis associated with the highest rate of readmission to the hospital and the emergency room and hospital mortality—controlling for cardiovascular disease, infection, sepsis, encephalopathy and “all the usual suspects associated with readmission,” says Katherine Tuttle, MD, clinical professor of medicine in the University of Washington Division of Nephrology.

The study, which included 676,000 hospitalized patients in Washington state in 2006 through 2008, was done in collaboration with Washington State University and Spokane-based Providence Sacred Heart Medical Center. Researchers found that the highest risk was found in patients on dialysis, but even in early stages of chronic kidney disease there was a significantly increased risk of readmissions and death, Dr. Tuttle said.¹

The reasons are not known.

“One reason we think is really important is this issue of medication management,” Dr. Tuttle says.

Researchers then did a pilot study showing that, at the time of discharge, if a pharmacist visited within the first week, the rates of readmission were reduced by 50 percent. “The goal of that visit was basically do what probably should have been done through the hospital, which is adjust drug doses properly for kidney function and address drug interaction,” Dr. Tuttle says.

The research team is working on a large study funded by the National Institutes of Health to validate those findings and look at a broader population of patients. This is more evidence pointing to the importance of handoffs, she says.

"These transitions in care are dangerous situations,” Dr. Tuttle says. “But they’re also opportunities for improvement. And I think anything we can do to enhance education management is likely to be very beneficial in people with chronic kidney disease.”

Hospitalists have "serious work to do in improving continuity in care, and handoffs in general,” she adds.

“So much of what they do in the hospital is influenced by kidney function, whether it’s the drugs they give or the diagnostic tests that they want to do,” she says. “I’m not being critical at all. It’s a new area, relatively speaking, and there are lots of opportunities for improvement in the system.”

Tom Collins is a freelance writer in South Florida.

Reference

1. Risks of subsequent hospitalization and death in patients with kidney disease. Clin J Am Soc Nephrol. 2012;7(3):409-416.

Need another reason to hone your skills in treating people with kidney disease?

Take a look at a study out of the University of Washington: Kidney disease, researchers there found, is the diagnosis associated with the highest rate of readmission to the hospital and the emergency room and hospital mortality—controlling for cardiovascular disease, infection, sepsis, encephalopathy and “all the usual suspects associated with readmission,” says Katherine Tuttle, MD, clinical professor of medicine in the University of Washington Division of Nephrology.

The study, which included 676,000 hospitalized patients in Washington state in 2006 through 2008, was done in collaboration with Washington State University and Spokane-based Providence Sacred Heart Medical Center. Researchers found that the highest risk was found in patients on dialysis, but even in early stages of chronic kidney disease there was a significantly increased risk of readmissions and death, Dr. Tuttle said.¹

The reasons are not known.

“One reason we think is really important is this issue of medication management,” Dr. Tuttle says.

Researchers then did a pilot study showing that, at the time of discharge, if a pharmacist visited within the first week, the rates of readmission were reduced by 50 percent. “The goal of that visit was basically do what probably should have been done through the hospital, which is adjust drug doses properly for kidney function and address drug interaction,” Dr. Tuttle says.

The research team is working on a large study funded by the National Institutes of Health to validate those findings and look at a broader population of patients. This is more evidence pointing to the importance of handoffs, she says.

"These transitions in care are dangerous situations,” Dr. Tuttle says. “But they’re also opportunities for improvement. And I think anything we can do to enhance education management is likely to be very beneficial in people with chronic kidney disease.”

Hospitalists have "serious work to do in improving continuity in care, and handoffs in general,” she adds.

“So much of what they do in the hospital is influenced by kidney function, whether it’s the drugs they give or the diagnostic tests that they want to do,” she says. “I’m not being critical at all. It’s a new area, relatively speaking, and there are lots of opportunities for improvement in the system.”

Tom Collins is a freelance writer in South Florida.

Reference

1. Risks of subsequent hospitalization and death in patients with kidney disease. Clin J Am Soc Nephrol. 2012;7(3):409-416.

Need another reason to hone your skills in treating people with kidney disease?

Take a look at a study out of the University of Washington: Kidney disease, researchers there found, is the diagnosis associated with the highest rate of readmission to the hospital and the emergency room and hospital mortality—controlling for cardiovascular disease, infection, sepsis, encephalopathy and “all the usual suspects associated with readmission,” says Katherine Tuttle, MD, clinical professor of medicine in the University of Washington Division of Nephrology.

The study, which included 676,000 hospitalized patients in Washington state in 2006 through 2008, was done in collaboration with Washington State University and Spokane-based Providence Sacred Heart Medical Center. Researchers found that the highest risk was found in patients on dialysis, but even in early stages of chronic kidney disease there was a significantly increased risk of readmissions and death, Dr. Tuttle said.¹

The reasons are not known.

“One reason we think is really important is this issue of medication management,” Dr. Tuttle says.

Researchers then did a pilot study showing that, at the time of discharge, if a pharmacist visited within the first week, the rates of readmission were reduced by 50 percent. “The goal of that visit was basically do what probably should have been done through the hospital, which is adjust drug doses properly for kidney function and address drug interaction,” Dr. Tuttle says.

The research team is working on a large study funded by the National Institutes of Health to validate those findings and look at a broader population of patients. This is more evidence pointing to the importance of handoffs, she says.

"These transitions in care are dangerous situations,” Dr. Tuttle says. “But they’re also opportunities for improvement. And I think anything we can do to enhance education management is likely to be very beneficial in people with chronic kidney disease.”

Hospitalists have "serious work to do in improving continuity in care, and handoffs in general,” she adds.

“So much of what they do in the hospital is influenced by kidney function, whether it’s the drugs they give or the diagnostic tests that they want to do,” she says. “I’m not being critical at all. It’s a new area, relatively speaking, and there are lots of opportunities for improvement in the system.”

Tom Collins is a freelance writer in South Florida.

Reference

1. Risks of subsequent hospitalization and death in patients with kidney disease. Clin J Am Soc Nephrol. 2012;7(3):409-416.

BOSTON  – Anemia developed significantly more often among patients with hepatitis C virus infection and compensated cirrhosis than among noncirrhotic patients during triple therapy in a randomized, open-label trial of treatment-naive patients, but in most instances the anemia was effectively treated.

In an anemia management subanalysis of a study comparing sustained virologic response (SVR) rates in cirrhotic and noncirrhotic patients treated with boceprevir (Victrelis), pegylated interferon alfa-2b (Peg-Intron), and ribavirin (RBV), 57% of patients with cirrhosis and anemia treated with a ribavirin dose reduction had an SVR, compared with 64% of those treated with erythropoietin. Among noncirrhotic patients with anemia, the respective SVR rates were 73% and 72%; none of the differences was significant, Dr. Eric J. Lawitz reported at the annual meeting of the American Association for the Study of Liver Diseases.

Courtesy US. Dept of Veterans Affairs

"Sustained viral responses are comparable in cirrhotic patients when anemia is managed by ribavirin dose reduction or erythropoietin," said Dr. Lawitz, medical director and principal investigator at Alamo Medical Research in San Antonio, Tex., adding that ribavirin dose reductions should be the initial strategy for managing anemia, followed, if necessary, by erythropoietin.

In the trial, 687 treatment-naive patients with hepatitis C virus (HCV) infections were treated for 4 weeks with pegylated interferon (PEG-IFN) alfa-2b and RBV, then 24 or 44 weeks of boceprevir added in. Baseline hemoglobin levels ranged from 12 g/dL to15 g/dL for women, and from 13 g/dL to15 g/dL for men.

Patients with a hemoglobin level approaching 10 g/dL or less (tested from baseline through week 48) were randomized to either ribavirin dose reduction (249 patients) in 200-mg increments (first increment of 400 mg for initial 1,400-mg daily doses) at the investigators’ discretion, or to erythropoietin (251 patients) at 40,000 U/wk, modifiable to 20,000 U/wk or 60,000 U/wk at the investigator’s discretion. The remaining patients received anemia prophylaxis but were not randomized.

If the hemoglobin level dropped to 8.5 g/dL, patients could receive the other treatment as a secondary intervention, and patients with a hemoglobin level of 7.5 g/dL were discontinued from all study drugs.

Primary efficacy measures for all patients (cirrhotic and noncirrhotic) in each anemia strategy group were identical, with 82% having an end-of-treatment response, 71% having an SVR, and 10% experiencing relapse.

Among cirrhotic vs. noncirrhotic patients, rates were 68% vs. 76% for end-of-treatment response , 55% vs. 64% for SVR, and 18% vs. 11% for relapse.

Patients with cirrhosis were significantly more likely to require a secondary anemia intervention (44% vs. 26%, P = .009). Among noncirrhotic patients (but not cirrhotic patients), a secondary anemia intervention was associated with a greater likelihood of SVR (80% vs. 70% for only one intervention, P = .05).

Serious adverse events occurred in 20% of cirrhotic patients and 12% of noncirrhotic patients, but only one study death occurred. The noncirrhotic patient died of a cardiac arrest, which was considered to be unrelated to therapy.

Treatment-emergent adverse events occurred in 3% of patients with cirrhosis and 2% of those without cirrhosis. Drug discontinuation for adverse events occurred in 17% of cirrhotic patients, and 16% of noncirrhotic patients.

Cirrhotic patients were more likely to have hemoglobin concentrations ranging from 6.5 to 8.0 g/dL than were noncirrhotic patients, but no patient in either group had a hemoglobin concentration below 6.5 g/dL.

Neutrophil counts in the range of 500-749/mm³ occurred in 24% of cirrhotic patients and 27% of noncirrhotic patients, and counts below 500/mm³ were seen in 20% and 12%.

Platelet counts from 25,000 to 49,999/mm³ occurred in 22% of cirrhotic patients and 2% of noncirrhotic patients. Counts below 25,000/mm³ were seen in 3% vs. less than 1%, respectively. Transfusion rates were similar between the groups.

The study was funded by Merck Sharp & Dohme, which manufactures boceprevir. Dr. Lawitz disclosed receiving grant and research support from the company.

BOSTON  – Anemia developed significantly more often among patients with hepatitis C virus infection and compensated cirrhosis than among noncirrhotic patients during triple therapy in a randomized, open-label trial of treatment-naive patients, but in most instances the anemia was effectively treated.

In an anemia management subanalysis of a study comparing sustained virologic response (SVR) rates in cirrhotic and noncirrhotic patients treated with boceprevir (Victrelis), pegylated interferon alfa-2b (Peg-Intron), and ribavirin (RBV), 57% of patients with cirrhosis and anemia treated with a ribavirin dose reduction had an SVR, compared with 64% of those treated with erythropoietin. Among noncirrhotic patients with anemia, the respective SVR rates were 73% and 72%; none of the differences was significant, Dr. Eric J. Lawitz reported at the annual meeting of the American Association for the Study of Liver Diseases.

Courtesy US. Dept of Veterans Affairs

"Sustained viral responses are comparable in cirrhotic patients when anemia is managed by ribavirin dose reduction or erythropoietin," said Dr. Lawitz, medical director and principal investigator at Alamo Medical Research in San Antonio, Tex., adding that ribavirin dose reductions should be the initial strategy for managing anemia, followed, if necessary, by erythropoietin.

In the trial, 687 treatment-naive patients with hepatitis C virus (HCV) infections were treated for 4 weeks with pegylated interferon (PEG-IFN) alfa-2b and RBV, then 24 or 44 weeks of boceprevir added in. Baseline hemoglobin levels ranged from 12 g/dL to15 g/dL for women, and from 13 g/dL to15 g/dL for men.

Patients with a hemoglobin level approaching 10 g/dL or less (tested from baseline through week 48) were randomized to either ribavirin dose reduction (249 patients) in 200-mg increments (first increment of 400 mg for initial 1,400-mg daily doses) at the investigators’ discretion, or to erythropoietin (251 patients) at 40,000 U/wk, modifiable to 20,000 U/wk or 60,000 U/wk at the investigator’s discretion. The remaining patients received anemia prophylaxis but were not randomized.

If the hemoglobin level dropped to 8.5 g/dL, patients could receive the other treatment as a secondary intervention, and patients with a hemoglobin level of 7.5 g/dL were discontinued from all study drugs.

Primary efficacy measures for all patients (cirrhotic and noncirrhotic) in each anemia strategy group were identical, with 82% having an end-of-treatment response, 71% having an SVR, and 10% experiencing relapse.

Among cirrhotic vs. noncirrhotic patients, rates were 68% vs. 76% for end-of-treatment response , 55% vs. 64% for SVR, and 18% vs. 11% for relapse.

Patients with cirrhosis were significantly more likely to require a secondary anemia intervention (44% vs. 26%, P = .009). Among noncirrhotic patients (but not cirrhotic patients), a secondary anemia intervention was associated with a greater likelihood of SVR (80% vs. 70% for only one intervention, P = .05).

Serious adverse events occurred in 20% of cirrhotic patients and 12% of noncirrhotic patients, but only one study death occurred. The noncirrhotic patient died of a cardiac arrest, which was considered to be unrelated to therapy.

Treatment-emergent adverse events occurred in 3% of patients with cirrhosis and 2% of those without cirrhosis. Drug discontinuation for adverse events occurred in 17% of cirrhotic patients, and 16% of noncirrhotic patients.

Cirrhotic patients were more likely to have hemoglobin concentrations ranging from 6.5 to 8.0 g/dL than were noncirrhotic patients, but no patient in either group had a hemoglobin concentration below 6.5 g/dL.

Neutrophil counts in the range of 500-749/mm³ occurred in 24% of cirrhotic patients and 27% of noncirrhotic patients, and counts below 500/mm³ were seen in 20% and 12%.

Platelet counts from 25,000 to 49,999/mm³ occurred in 22% of cirrhotic patients and 2% of noncirrhotic patients. Counts below 25,000/mm³ were seen in 3% vs. less than 1%, respectively. Transfusion rates were similar between the groups.

The study was funded by Merck Sharp & Dohme, which manufactures boceprevir. Dr. Lawitz disclosed receiving grant and research support from the company.

BOSTON  – Anemia developed significantly more often among patients with hepatitis C virus infection and compensated cirrhosis than among noncirrhotic patients during triple therapy in a randomized, open-label trial of treatment-naive patients, but in most instances the anemia was effectively treated.

In an anemia management subanalysis of a study comparing sustained virologic response (SVR) rates in cirrhotic and noncirrhotic patients treated with boceprevir (Victrelis), pegylated interferon alfa-2b (Peg-Intron), and ribavirin (RBV), 57% of patients with cirrhosis and anemia treated with a ribavirin dose reduction had an SVR, compared with 64% of those treated with erythropoietin. Among noncirrhotic patients with anemia, the respective SVR rates were 73% and 72%; none of the differences was significant, Dr. Eric J. Lawitz reported at the annual meeting of the American Association for the Study of Liver Diseases.

Courtesy US. Dept of Veterans Affairs

"Sustained viral responses are comparable in cirrhotic patients when anemia is managed by ribavirin dose reduction or erythropoietin," said Dr. Lawitz, medical director and principal investigator at Alamo Medical Research in San Antonio, Tex., adding that ribavirin dose reductions should be the initial strategy for managing anemia, followed, if necessary, by erythropoietin.

In the trial, 687 treatment-naive patients with hepatitis C virus (HCV) infections were treated for 4 weeks with pegylated interferon (PEG-IFN) alfa-2b and RBV, then 24 or 44 weeks of boceprevir added in. Baseline hemoglobin levels ranged from 12 g/dL to15 g/dL for women, and from 13 g/dL to15 g/dL for men.

Patients with a hemoglobin level approaching 10 g/dL or less (tested from baseline through week 48) were randomized to either ribavirin dose reduction (249 patients) in 200-mg increments (first increment of 400 mg for initial 1,400-mg daily doses) at the investigators’ discretion, or to erythropoietin (251 patients) at 40,000 U/wk, modifiable to 20,000 U/wk or 60,000 U/wk at the investigator’s discretion. The remaining patients received anemia prophylaxis but were not randomized.

If the hemoglobin level dropped to 8.5 g/dL, patients could receive the other treatment as a secondary intervention, and patients with a hemoglobin level of 7.5 g/dL were discontinued from all study drugs.

Primary efficacy measures for all patients (cirrhotic and noncirrhotic) in each anemia strategy group were identical, with 82% having an end-of-treatment response, 71% having an SVR, and 10% experiencing relapse.

Among cirrhotic vs. noncirrhotic patients, rates were 68% vs. 76% for end-of-treatment response , 55% vs. 64% for SVR, and 18% vs. 11% for relapse.

Patients with cirrhosis were significantly more likely to require a secondary anemia intervention (44% vs. 26%, P = .009). Among noncirrhotic patients (but not cirrhotic patients), a secondary anemia intervention was associated with a greater likelihood of SVR (80% vs. 70% for only one intervention, P = .05).

Serious adverse events occurred in 20% of cirrhotic patients and 12% of noncirrhotic patients, but only one study death occurred. The noncirrhotic patient died of a cardiac arrest, which was considered to be unrelated to therapy.

Treatment-emergent adverse events occurred in 3% of patients with cirrhosis and 2% of those without cirrhosis. Drug discontinuation for adverse events occurred in 17% of cirrhotic patients, and 16% of noncirrhotic patients.

Cirrhotic patients were more likely to have hemoglobin concentrations ranging from 6.5 to 8.0 g/dL than were noncirrhotic patients, but no patient in either group had a hemoglobin concentration below 6.5 g/dL.

Neutrophil counts in the range of 500-749/mm³ occurred in 24% of cirrhotic patients and 27% of noncirrhotic patients, and counts below 500/mm³ were seen in 20% and 12%.

Platelet counts from 25,000 to 49,999/mm³ occurred in 22% of cirrhotic patients and 2% of noncirrhotic patients. Counts below 25,000/mm³ were seen in 3% vs. less than 1%, respectively. Transfusion rates were similar between the groups.

The study was funded by Merck Sharp & Dohme, which manufactures boceprevir. Dr. Lawitz disclosed receiving grant and research support from the company.

ATLANTA – More than one-fifth of patients with relapsed or refractory mantle cell lymphoma had a complete response to single-agent therapy with experimental ibrutinib, and another two-fifths had a partial response, investigators reported.

"Colleagues, this is the highest response rate ever reported, ever achieved by one single drug in the history of relapsed mantle cell lymphoma," Dr. Michael Wang told attendees at the annual meeting of the American Society of Hematology.

Dr. Wang’s evident excitement about the data came exactly 1 year to the day after he announced preliminary results of the phase II trial at ASH 2011. At that time, the drug was known only as PCI-32765.

Those early data showed that ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK) expressed in several hematologic malignancies, induced complete response in 16% and partial response in 53% of patients evaluated at that time for a combined overall response rate of 69%.

The drug demonstrated efficacy against bulky disease, and its effects in early studies appeared to be independent of the MCL [Mantle Cell Lymphoma] International Prognostic Index (MIPI) score.

At this year’s meeting, Dr. Wang of the University of Texas M.D. Anderson Cancer Center, Houston, reported that in an efficacy cohort of 110 patients, 22% had a complete response and 46% a partial response. Among patients who had previously been treated with bortezomib (Velcade), 23% had a complete response, and 49% had a partial response. In bortezomib-naive patients the response rates were 21% and 44%, respectively.

At 9.2 months of follow-up (data cutoff Sept. 21, 2012), the median duration of response had not been reached. Median progression-free survival was 13.9 months.

Ibrutinib was well tolerated

BTK, an essential element of the B-cell antigen receptor–signaling pathway, is expressed in several hematologic malignancies, including lymphoma and chronic lymphocytic leukemia, for which positive clinical trial data were also presented at the meeting. Ibrutinib blocks receptor signaling and induces apoptosis, as well as mantle cell migration and adhesion. It has been shown in in vitro studies to block pERK, pJNK, and NF-KappaB pathways in MCL cell lines.

Dr. Wang and colleagues at 18 U.S. and European centers enrolled patients with confirmed overexpression of cyclin D1 or the 11;14 translocation and measurable disease. The patients had not been able to achieve at least a partial response to prior therapy, or had disease progression following their most recent treatment regimen. All had at least one, but not more than five prior lines of therapy, and adequate end-organ function, and Eastern Cooperative Oncology Group performance status of 2 or lower.

The drug was generally well tolerated, he said, with neutropenia, thrombocytopenia, and anemia being the most frequent hematologic toxicities, and diarrhea, fatigue, nausea, and respiratory tract infections being the most common nonhematologic adverse events.

Dr. Wang noted that longer follow-up of data on 51 patients in the cohort that he presented at ASH 2011 show improvement in complete response rates. The initial rates among bortezomib-naive, bortezomib experienced, and all patients were 16%, 15%, and 16%, respectively, at a median of 3.7 months. In the current follow-up of these patients, however (median 14.7 months), the complete response rates had improved to 40%, 38%, and 39%, respectively, with respective overall response rates of 77%, 71%, and 75%. He called the gradual increase in complete response rates the "phenomenon of incremental response."

Phenomenon of incremental response

Dr. Andrew D. Zelenetz of Memorial Sloan-Kettering Cancer Center, New York, said after Dr. Wang’s presentation that the "phenomenon of incremental response" Dr. Wang described is not really a phenomenon at all.

"The reason you’re giving the drug continuously is that you expect to see a better response," he said. "It’s not unique to this drug, but in rituximab it’s seen when you stop the drug, in lenalidomide it’s seen when you stop the drug, and in radioimmunotherapy it’s seen when you stop the drug. So incremental response is a well described phenomenon in lymphomas," Dr. Zelenetz said.

"This has been just an interim analysis our data. We look forward to updating you with the final results of this clinical trial with excitement, caution, and confidence," Dr.Wang said.

The study was supported by Pharmacyclics. Dr. Wang is on the scientific advisory board of the company. Dr. Zelenetz had no relevant disclosures.

ATLANTA – More than one-fifth of patients with relapsed or refractory mantle cell lymphoma had a complete response to single-agent therapy with experimental ibrutinib, and another two-fifths had a partial response, investigators reported.

"Colleagues, this is the highest response rate ever reported, ever achieved by one single drug in the history of relapsed mantle cell lymphoma," Dr. Michael Wang told attendees at the annual meeting of the American Society of Hematology.

Dr. Wang’s evident excitement about the data came exactly 1 year to the day after he announced preliminary results of the phase II trial at ASH 2011. At that time, the drug was known only as PCI-32765.

Those early data showed that ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK) expressed in several hematologic malignancies, induced complete response in 16% and partial response in 53% of patients evaluated at that time for a combined overall response rate of 69%.

The drug demonstrated efficacy against bulky disease, and its effects in early studies appeared to be independent of the MCL [Mantle Cell Lymphoma] International Prognostic Index (MIPI) score.

At this year’s meeting, Dr. Wang of the University of Texas M.D. Anderson Cancer Center, Houston, reported that in an efficacy cohort of 110 patients, 22% had a complete response and 46% a partial response. Among patients who had previously been treated with bortezomib (Velcade), 23% had a complete response, and 49% had a partial response. In bortezomib-naive patients the response rates were 21% and 44%, respectively.

At 9.2 months of follow-up (data cutoff Sept. 21, 2012), the median duration of response had not been reached. Median progression-free survival was 13.9 months.

Ibrutinib was well tolerated

BTK, an essential element of the B-cell antigen receptor–signaling pathway, is expressed in several hematologic malignancies, including lymphoma and chronic lymphocytic leukemia, for which positive clinical trial data were also presented at the meeting. Ibrutinib blocks receptor signaling and induces apoptosis, as well as mantle cell migration and adhesion. It has been shown in in vitro studies to block pERK, pJNK, and NF-KappaB pathways in MCL cell lines.

Dr. Wang and colleagues at 18 U.S. and European centers enrolled patients with confirmed overexpression of cyclin D1 or the 11;14 translocation and measurable disease. The patients had not been able to achieve at least a partial response to prior therapy, or had disease progression following their most recent treatment regimen. All had at least one, but not more than five prior lines of therapy, and adequate end-organ function, and Eastern Cooperative Oncology Group performance status of 2 or lower.

The drug was generally well tolerated, he said, with neutropenia, thrombocytopenia, and anemia being the most frequent hematologic toxicities, and diarrhea, fatigue, nausea, and respiratory tract infections being the most common nonhematologic adverse events.

Dr. Wang noted that longer follow-up of data on 51 patients in the cohort that he presented at ASH 2011 show improvement in complete response rates. The initial rates among bortezomib-naive, bortezomib experienced, and all patients were 16%, 15%, and 16%, respectively, at a median of 3.7 months. In the current follow-up of these patients, however (median 14.7 months), the complete response rates had improved to 40%, 38%, and 39%, respectively, with respective overall response rates of 77%, 71%, and 75%. He called the gradual increase in complete response rates the "phenomenon of incremental response."

Phenomenon of incremental response

Dr. Andrew D. Zelenetz of Memorial Sloan-Kettering Cancer Center, New York, said after Dr. Wang’s presentation that the "phenomenon of incremental response" Dr. Wang described is not really a phenomenon at all.

"The reason you’re giving the drug continuously is that you expect to see a better response," he said. "It’s not unique to this drug, but in rituximab it’s seen when you stop the drug, in lenalidomide it’s seen when you stop the drug, and in radioimmunotherapy it’s seen when you stop the drug. So incremental response is a well described phenomenon in lymphomas," Dr. Zelenetz said.

"This has been just an interim analysis our data. We look forward to updating you with the final results of this clinical trial with excitement, caution, and confidence," Dr.Wang said.

The study was supported by Pharmacyclics. Dr. Wang is on the scientific advisory board of the company. Dr. Zelenetz had no relevant disclosures.

ATLANTA – More than one-fifth of patients with relapsed or refractory mantle cell lymphoma had a complete response to single-agent therapy with experimental ibrutinib, and another two-fifths had a partial response, investigators reported.

"Colleagues, this is the highest response rate ever reported, ever achieved by one single drug in the history of relapsed mantle cell lymphoma," Dr. Michael Wang told attendees at the annual meeting of the American Society of Hematology.

Dr. Wang’s evident excitement about the data came exactly 1 year to the day after he announced preliminary results of the phase II trial at ASH 2011. At that time, the drug was known only as PCI-32765.

Those early data showed that ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK) expressed in several hematologic malignancies, induced complete response in 16% and partial response in 53% of patients evaluated at that time for a combined overall response rate of 69%.

The drug demonstrated efficacy against bulky disease, and its effects in early studies appeared to be independent of the MCL [Mantle Cell Lymphoma] International Prognostic Index (MIPI) score.

At this year’s meeting, Dr. Wang of the University of Texas M.D. Anderson Cancer Center, Houston, reported that in an efficacy cohort of 110 patients, 22% had a complete response and 46% a partial response. Among patients who had previously been treated with bortezomib (Velcade), 23% had a complete response, and 49% had a partial response. In bortezomib-naive patients the response rates were 21% and 44%, respectively.

At 9.2 months of follow-up (data cutoff Sept. 21, 2012), the median duration of response had not been reached. Median progression-free survival was 13.9 months.

Ibrutinib was well tolerated

BTK, an essential element of the B-cell antigen receptor–signaling pathway, is expressed in several hematologic malignancies, including lymphoma and chronic lymphocytic leukemia, for which positive clinical trial data were also presented at the meeting. Ibrutinib blocks receptor signaling and induces apoptosis, as well as mantle cell migration and adhesion. It has been shown in in vitro studies to block pERK, pJNK, and NF-KappaB pathways in MCL cell lines.

Dr. Wang and colleagues at 18 U.S. and European centers enrolled patients with confirmed overexpression of cyclin D1 or the 11;14 translocation and measurable disease. The patients had not been able to achieve at least a partial response to prior therapy, or had disease progression following their most recent treatment regimen. All had at least one, but not more than five prior lines of therapy, and adequate end-organ function, and Eastern Cooperative Oncology Group performance status of 2 or lower.

The drug was generally well tolerated, he said, with neutropenia, thrombocytopenia, and anemia being the most frequent hematologic toxicities, and diarrhea, fatigue, nausea, and respiratory tract infections being the most common nonhematologic adverse events.

Dr. Wang noted that longer follow-up of data on 51 patients in the cohort that he presented at ASH 2011 show improvement in complete response rates. The initial rates among bortezomib-naive, bortezomib experienced, and all patients were 16%, 15%, and 16%, respectively, at a median of 3.7 months. In the current follow-up of these patients, however (median 14.7 months), the complete response rates had improved to 40%, 38%, and 39%, respectively, with respective overall response rates of 77%, 71%, and 75%. He called the gradual increase in complete response rates the "phenomenon of incremental response."

Phenomenon of incremental response

Dr. Andrew D. Zelenetz of Memorial Sloan-Kettering Cancer Center, New York, said after Dr. Wang’s presentation that the "phenomenon of incremental response" Dr. Wang described is not really a phenomenon at all.

"The reason you’re giving the drug continuously is that you expect to see a better response," he said. "It’s not unique to this drug, but in rituximab it’s seen when you stop the drug, in lenalidomide it’s seen when you stop the drug, and in radioimmunotherapy it’s seen when you stop the drug. So incremental response is a well described phenomenon in lymphomas," Dr. Zelenetz said.

"This has been just an interim analysis our data. We look forward to updating you with the final results of this clinical trial with excitement, caution, and confidence," Dr.Wang said.

The study was supported by Pharmacyclics. Dr. Wang is on the scientific advisory board of the company. Dr. Zelenetz had no relevant disclosures.

ATLANTA – An extra year of apixaban reduced the risk of recurrent events in patients with venous thromboembolism by 80%, while keeping major bleeding rates in line with placebo in the randomized AMPLIFY-EXT trial.

The number needed to treat with apixaban (Eliquis) to prevent one fatal or nonfatal recurrent VTE was only 14, while the number needed to treat to cause one episode of major or clinically relevant nonmajor bleeding was 200, Dr. Giancarlo Agnelli reported in a late-breaking abstract at the annual meeting of the American Society of Hematology.

Patrice Wendling/IMNG Medical Media

"We really believe this study, for its design and results, is a remarkable achievement, and [may lead to a] change in clinical practice," he said during a press briefing at the meeting.

Apixaban was approved by the Food and Drug Adminis­tration in late December for the prevention of stroke and systemic embolism in pa­tients with non-valvular atri­al fibrillation, based largely on data demonstrating superiority to warfarin in patients with AF in the ARISTOTLE trial.*

In the meantime, the results of AMPLIFY-EXT (Apixaban After the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy–Extended Treatment) provide some guidance for physicians uncertain about whether to extend or stop standard anticoagulation therapy in patients with VTE in the absence of recurrent events. Stopping warfarin therapy increases the risk of recurrent VTE by up to 10% in patients without reversible risk factors, but also requires frequent laboratory monitoring and increases the risk of bleeding.

Apixaban, an oral factor Xa inhibitor, is given in fixed doses without the need for laboratory monitoring, said Dr. Agnelli, director of the internal and cardiovascular medicine/stroke unit at the University of Perugia, Italy.

Given the efficacy demonstrated in AMPLIFY-EXT, apixaban may also be an attractive option for those VTE patients with renal impairment, because it is the least dependent on renal clearance compared with two other fixed-dose anticoagulants, rivaroxaban (Xarelto) and dabigatran (Pradaxa), said press briefing moderator Dr. Agnes Lee, medical director of the thrombosis program and associate professor of medicine at the University of British Columbia, Vancouver, and Vancouver Coastal Health.

Notably, a recent prespecified substudy of ARISTOLE demonstrated that apixaban produced 35%-52% fewer major bleeding events in patients with renal dysfunction and atrial fibrillation.

The double-blind AMPLIFY-EXT trial randomized 842 patients to apixaban 2.5 mg, 815 to apixaban 5 mg, and 829 to placebo, all twice daily for 12 months. Three-fourths had an initial diagnosis of deep vein thrombosis and one-fourth pulmonary embolism. All had received 6-12 months of anticoagulation therapy and reached clinical equipoise about the continuation or cessation of anticoagulation therapy.

VTE was associated with a transient or reversible risk factor in less than 10% of patients. Two patients from each apixaban group were excluded from the intention-to-treat efficacy analysis. Their average age was roughly 56.

The composite primary efficacy endpoint of symptomatic VTE recurrence or all-cause death occurred in 3.8% of patients on apixaban 2.5 mg and in 4.2% of patients on apixaban 5 mg, compared with 11.6% of patients given placebo, Dr. Agnelli said.

Symptomatic recurrent VTE or death from VTE occurred in 1.7% of patients in both apixaban groups vs. 8.8% of placebo-treated patients.

Major bleeding was reported in 0.2% of the 2.5-mg apixaban group, 0.1% of the 5-mg group, and 0.5% of the placebo group. Clinically relevant nonmajor bleeding rates were slightly higher at 3.0% and 4.2% in the apixaban groups vs. 2.3% in the placebo group, he said.

Further study will be needed to determine if the results can be directly applied to cancer patients who face an increased risk of VTE because of the disease, as only about 2% of the study population had active cancer, Dr. Agnelli said in an interview.

The study was simultaneously published in the New England Journal of Medicine (2012 Dec. 8 [doi: 10.1056/NEJMoa1207541]).

AMPLIFY-EXT was funded by Bristol-Myers Squibb and Pfizer. Dr. Agnelli reported commercial relationships with Bristol-Myers Squibb, Daiichi Sankyo, and other companies. His coauthors reported relationships with the study sponsors. Dr. Lee disclosed consulting for Bristol-Myers Squibb.

*This article was updated January 2, 2013.

ATLANTA – An extra year of apixaban reduced the risk of recurrent events in patients with venous thromboembolism by 80%, while keeping major bleeding rates in line with placebo in the randomized AMPLIFY-EXT trial.

The number needed to treat with apixaban (Eliquis) to prevent one fatal or nonfatal recurrent VTE was only 14, while the number needed to treat to cause one episode of major or clinically relevant nonmajor bleeding was 200, Dr. Giancarlo Agnelli reported in a late-breaking abstract at the annual meeting of the American Society of Hematology.

Patrice Wendling/IMNG Medical Media

"We really believe this study, for its design and results, is a remarkable achievement, and [may lead to a] change in clinical practice," he said during a press briefing at the meeting.

Apixaban was approved by the Food and Drug Adminis­tration in late December for the prevention of stroke and systemic embolism in pa­tients with non-valvular atri­al fibrillation, based largely on data demonstrating superiority to warfarin in patients with AF in the ARISTOTLE trial.*

In the meantime, the results of AMPLIFY-EXT (Apixaban After the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy–Extended Treatment) provide some guidance for physicians uncertain about whether to extend or stop standard anticoagulation therapy in patients with VTE in the absence of recurrent events. Stopping warfarin therapy increases the risk of recurrent VTE by up to 10% in patients without reversible risk factors, but also requires frequent laboratory monitoring and increases the risk of bleeding.

Apixaban, an oral factor Xa inhibitor, is given in fixed doses without the need for laboratory monitoring, said Dr. Agnelli, director of the internal and cardiovascular medicine/stroke unit at the University of Perugia, Italy.

Given the efficacy demonstrated in AMPLIFY-EXT, apixaban may also be an attractive option for those VTE patients with renal impairment, because it is the least dependent on renal clearance compared with two other fixed-dose anticoagulants, rivaroxaban (Xarelto) and dabigatran (Pradaxa), said press briefing moderator Dr. Agnes Lee, medical director of the thrombosis program and associate professor of medicine at the University of British Columbia, Vancouver, and Vancouver Coastal Health.

Notably, a recent prespecified substudy of ARISTOLE demonstrated that apixaban produced 35%-52% fewer major bleeding events in patients with renal dysfunction and atrial fibrillation.

The double-blind AMPLIFY-EXT trial randomized 842 patients to apixaban 2.5 mg, 815 to apixaban 5 mg, and 829 to placebo, all twice daily for 12 months. Three-fourths had an initial diagnosis of deep vein thrombosis and one-fourth pulmonary embolism. All had received 6-12 months of anticoagulation therapy and reached clinical equipoise about the continuation or cessation of anticoagulation therapy.

VTE was associated with a transient or reversible risk factor in less than 10% of patients. Two patients from each apixaban group were excluded from the intention-to-treat efficacy analysis. Their average age was roughly 56.

The composite primary efficacy endpoint of symptomatic VTE recurrence or all-cause death occurred in 3.8% of patients on apixaban 2.5 mg and in 4.2% of patients on apixaban 5 mg, compared with 11.6% of patients given placebo, Dr. Agnelli said.

Symptomatic recurrent VTE or death from VTE occurred in 1.7% of patients in both apixaban groups vs. 8.8% of placebo-treated patients.

Major bleeding was reported in 0.2% of the 2.5-mg apixaban group, 0.1% of the 5-mg group, and 0.5% of the placebo group. Clinically relevant nonmajor bleeding rates were slightly higher at 3.0% and 4.2% in the apixaban groups vs. 2.3% in the placebo group, he said.

Further study will be needed to determine if the results can be directly applied to cancer patients who face an increased risk of VTE because of the disease, as only about 2% of the study population had active cancer, Dr. Agnelli said in an interview.

The study was simultaneously published in the New England Journal of Medicine (2012 Dec. 8 [doi: 10.1056/NEJMoa1207541]).

AMPLIFY-EXT was funded by Bristol-Myers Squibb and Pfizer. Dr. Agnelli reported commercial relationships with Bristol-Myers Squibb, Daiichi Sankyo, and other companies. His coauthors reported relationships with the study sponsors. Dr. Lee disclosed consulting for Bristol-Myers Squibb.

*This article was updated January 2, 2013.

ATLANTA – An extra year of apixaban reduced the risk of recurrent events in patients with venous thromboembolism by 80%, while keeping major bleeding rates in line with placebo in the randomized AMPLIFY-EXT trial.

The number needed to treat with apixaban (Eliquis) to prevent one fatal or nonfatal recurrent VTE was only 14, while the number needed to treat to cause one episode of major or clinically relevant nonmajor bleeding was 200, Dr. Giancarlo Agnelli reported in a late-breaking abstract at the annual meeting of the American Society of Hematology.

Patrice Wendling/IMNG Medical Media

"We really believe this study, for its design and results, is a remarkable achievement, and [may lead to a] change in clinical practice," he said during a press briefing at the meeting.

Apixaban was approved by the Food and Drug Adminis­tration in late December for the prevention of stroke and systemic embolism in pa­tients with non-valvular atri­al fibrillation, based largely on data demonstrating superiority to warfarin in patients with AF in the ARISTOTLE trial.*

In the meantime, the results of AMPLIFY-EXT (Apixaban After the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy–Extended Treatment) provide some guidance for physicians uncertain about whether to extend or stop standard anticoagulation therapy in patients with VTE in the absence of recurrent events. Stopping warfarin therapy increases the risk of recurrent VTE by up to 10% in patients without reversible risk factors, but also requires frequent laboratory monitoring and increases the risk of bleeding.

Apixaban, an oral factor Xa inhibitor, is given in fixed doses without the need for laboratory monitoring, said Dr. Agnelli, director of the internal and cardiovascular medicine/stroke unit at the University of Perugia, Italy.

Given the efficacy demonstrated in AMPLIFY-EXT, apixaban may also be an attractive option for those VTE patients with renal impairment, because it is the least dependent on renal clearance compared with two other fixed-dose anticoagulants, rivaroxaban (Xarelto) and dabigatran (Pradaxa), said press briefing moderator Dr. Agnes Lee, medical director of the thrombosis program and associate professor of medicine at the University of British Columbia, Vancouver, and Vancouver Coastal Health.

Notably, a recent prespecified substudy of ARISTOLE demonstrated that apixaban produced 35%-52% fewer major bleeding events in patients with renal dysfunction and atrial fibrillation.

The double-blind AMPLIFY-EXT trial randomized 842 patients to apixaban 2.5 mg, 815 to apixaban 5 mg, and 829 to placebo, all twice daily for 12 months. Three-fourths had an initial diagnosis of deep vein thrombosis and one-fourth pulmonary embolism. All had received 6-12 months of anticoagulation therapy and reached clinical equipoise about the continuation or cessation of anticoagulation therapy.

VTE was associated with a transient or reversible risk factor in less than 10% of patients. Two patients from each apixaban group were excluded from the intention-to-treat efficacy analysis. Their average age was roughly 56.

The composite primary efficacy endpoint of symptomatic VTE recurrence or all-cause death occurred in 3.8% of patients on apixaban 2.5 mg and in 4.2% of patients on apixaban 5 mg, compared with 11.6% of patients given placebo, Dr. Agnelli said.

Symptomatic recurrent VTE or death from VTE occurred in 1.7% of patients in both apixaban groups vs. 8.8% of placebo-treated patients.

Major bleeding was reported in 0.2% of the 2.5-mg apixaban group, 0.1% of the 5-mg group, and 0.5% of the placebo group. Clinically relevant nonmajor bleeding rates were slightly higher at 3.0% and 4.2% in the apixaban groups vs. 2.3% in the placebo group, he said.

Further study will be needed to determine if the results can be directly applied to cancer patients who face an increased risk of VTE because of the disease, as only about 2% of the study population had active cancer, Dr. Agnelli said in an interview.

The study was simultaneously published in the New England Journal of Medicine (2012 Dec. 8 [doi: 10.1056/NEJMoa1207541]).

AMPLIFY-EXT was funded by Bristol-Myers Squibb and Pfizer. Dr. Agnelli reported commercial relationships with Bristol-Myers Squibb, Daiichi Sankyo, and other companies. His coauthors reported relationships with the study sponsors. Dr. Lee disclosed consulting for Bristol-Myers Squibb.

*This article was updated January 2, 2013.

An author of a new study associating the hypnotic zolpidem (Ambien) with higher rates of patient falls says hospitalists should keep the popular drug’s risks front of mind.

The retrospective cohort study in the Journal of Hospital Medicine, “Zolpidem is Independently Associated with Increased Risk of Inpatient Falls,” found that the rate of falls increased nearly six times among patients taking the sleep agent. The research team at the Center for Sleep Medicine at the Mayo Clinic in Rochester, N.Y., calculated one additional fall for every 55 admitted patients who were administered the treatment.

“What this says to me is if one is going to use zolpidem, you have to be aware you’re increasing the risk of fall,” says sleep specialist Timothy Morgenthaler, MD, the Mayo Clinic’s chief patient officer. “Knowledgeable of that, one ought to consider whether there are alternatives or whether the risks outweigh the goal in that setting.”

Dr. Morgenthaler says zolpidem is the most commonly prescribed hypnotic at his hospital, and believes it to be the most common treatment in the U.S. He began studying the issue after nurses reported that it appeared patients were falling after taking the agent. In response to the study, Mayo Clinic removed zolpidem from many of its admission order sets and attempted to help improve patient sleep via other methods, including noise reduction.

“We haven’t removed it from our formulary, and I’m not saying it doesn’t have a role in some points,” he says, “but rather than encouraging it as an option in patients being admitted into the patient, we’re choosing instead now to encourage nonpharmacologic sleep enhancements.” 

Visit our website for more information about HM’s approach to patient falls.

 

An author of a new study associating the hypnotic zolpidem (Ambien) with higher rates of patient falls says hospitalists should keep the popular drug’s risks front of mind.

The retrospective cohort study in the Journal of Hospital Medicine, “Zolpidem is Independently Associated with Increased Risk of Inpatient Falls,” found that the rate of falls increased nearly six times among patients taking the sleep agent. The research team at the Center for Sleep Medicine at the Mayo Clinic in Rochester, N.Y., calculated one additional fall for every 55 admitted patients who were administered the treatment.

“What this says to me is if one is going to use zolpidem, you have to be aware you’re increasing the risk of fall,” says sleep specialist Timothy Morgenthaler, MD, the Mayo Clinic’s chief patient officer. “Knowledgeable of that, one ought to consider whether there are alternatives or whether the risks outweigh the goal in that setting.”

Dr. Morgenthaler says zolpidem is the most commonly prescribed hypnotic at his hospital, and believes it to be the most common treatment in the U.S. He began studying the issue after nurses reported that it appeared patients were falling after taking the agent. In response to the study, Mayo Clinic removed zolpidem from many of its admission order sets and attempted to help improve patient sleep via other methods, including noise reduction.

“We haven’t removed it from our formulary, and I’m not saying it doesn’t have a role in some points,” he says, “but rather than encouraging it as an option in patients being admitted into the patient, we’re choosing instead now to encourage nonpharmacologic sleep enhancements.” 

Visit our website for more information about HM’s approach to patient falls.

 

An author of a new study associating the hypnotic zolpidem (Ambien) with higher rates of patient falls says hospitalists should keep the popular drug’s risks front of mind.

The retrospective cohort study in the Journal of Hospital Medicine, “Zolpidem is Independently Associated with Increased Risk of Inpatient Falls,” found that the rate of falls increased nearly six times among patients taking the sleep agent. The research team at the Center for Sleep Medicine at the Mayo Clinic in Rochester, N.Y., calculated one additional fall for every 55 admitted patients who were administered the treatment.

“What this says to me is if one is going to use zolpidem, you have to be aware you’re increasing the risk of fall,” says sleep specialist Timothy Morgenthaler, MD, the Mayo Clinic’s chief patient officer. “Knowledgeable of that, one ought to consider whether there are alternatives or whether the risks outweigh the goal in that setting.”

Dr. Morgenthaler says zolpidem is the most commonly prescribed hypnotic at his hospital, and believes it to be the most common treatment in the U.S. He began studying the issue after nurses reported that it appeared patients were falling after taking the agent. In response to the study, Mayo Clinic removed zolpidem from many of its admission order sets and attempted to help improve patient sleep via other methods, including noise reduction.

“We haven’t removed it from our formulary, and I’m not saying it doesn’t have a role in some points,” he says, “but rather than encouraging it as an option in patients being admitted into the patient, we’re choosing instead now to encourage nonpharmacologic sleep enhancements.” 

Visit our website for more information about HM’s approach to patient falls.

 

Two recent studies have reached the same surprising conclusion: Adherence to national quality and performance guidelines does not translate into reduced readmissions rates.

Sula Mazimba, MD, MPH, and colleagues at Kettering Medical Center in Kettering, Ohio, focused on congestive heart failure (CHF) patients, documenting compliance with four core CHF performance measures at discharge and subsequent 30-day readmissions. Only one measure-assessment of left ventricular function-had a significant association with readmissions.

A second study published the same month looked at a wider range of diagnoses in a Medicare population at more than 2,000 hospitals nationwide. That study reached similar conclusions about the disconnect between hospitals that followed Hospital Compare process quality measures and their readmission rates.

Dr. Mazimba says hospitalists and other physicians involved in quality improvement (QI) should be more involved in defining quality measures that reflect quality of care for their patients.

“We should be looking for parameters that have a higher yield for outcomes, such as preventing readmissions,” he says, encouraging better symptom management before the CHF patient is hospitalized and enhanced coordination of care after discharge.

Alpesh Amin, MD, MBA, SFHM, professor and chair of the department of medicine and executive director of the hospitalist program at the University of California at Irvine, says the findings are important, but he adds that the core quality measures studied were never designed to address readmissions.

“The challenge is to find a way to connect the dots between the core measures and readmissions,” he says.

Learn more about the four "core" heart failure quality measures for hospitals by visiting the Resource Rooms on the SHM website, or check out this 80-page implementation guide, “Improving Heart Failure Care for Hospitalized Patients [PDF],” also available on SHM’s website.

Read The Hospitalist columnist Win Whitcomb’s take on readmissions penalty programs.

 

Two recent studies have reached the same surprising conclusion: Adherence to national quality and performance guidelines does not translate into reduced readmissions rates.

Sula Mazimba, MD, MPH, and colleagues at Kettering Medical Center in Kettering, Ohio, focused on congestive heart failure (CHF) patients, documenting compliance with four core CHF performance measures at discharge and subsequent 30-day readmissions. Only one measure-assessment of left ventricular function-had a significant association with readmissions.

A second study published the same month looked at a wider range of diagnoses in a Medicare population at more than 2,000 hospitals nationwide. That study reached similar conclusions about the disconnect between hospitals that followed Hospital Compare process quality measures and their readmission rates.

Dr. Mazimba says hospitalists and other physicians involved in quality improvement (QI) should be more involved in defining quality measures that reflect quality of care for their patients.

“We should be looking for parameters that have a higher yield for outcomes, such as preventing readmissions,” he says, encouraging better symptom management before the CHF patient is hospitalized and enhanced coordination of care after discharge.

Alpesh Amin, MD, MBA, SFHM, professor and chair of the department of medicine and executive director of the hospitalist program at the University of California at Irvine, says the findings are important, but he adds that the core quality measures studied were never designed to address readmissions.

“The challenge is to find a way to connect the dots between the core measures and readmissions,” he says.

Learn more about the four "core" heart failure quality measures for hospitals by visiting the Resource Rooms on the SHM website, or check out this 80-page implementation guide, “Improving Heart Failure Care for Hospitalized Patients [PDF],” also available on SHM’s website.

Read The Hospitalist columnist Win Whitcomb’s take on readmissions penalty programs.

 

Two recent studies have reached the same surprising conclusion: Adherence to national quality and performance guidelines does not translate into reduced readmissions rates.

Sula Mazimba, MD, MPH, and colleagues at Kettering Medical Center in Kettering, Ohio, focused on congestive heart failure (CHF) patients, documenting compliance with four core CHF performance measures at discharge and subsequent 30-day readmissions. Only one measure-assessment of left ventricular function-had a significant association with readmissions.

A second study published the same month looked at a wider range of diagnoses in a Medicare population at more than 2,000 hospitals nationwide. That study reached similar conclusions about the disconnect between hospitals that followed Hospital Compare process quality measures and their readmission rates.

Dr. Mazimba says hospitalists and other physicians involved in quality improvement (QI) should be more involved in defining quality measures that reflect quality of care for their patients.

“We should be looking for parameters that have a higher yield for outcomes, such as preventing readmissions,” he says, encouraging better symptom management before the CHF patient is hospitalized and enhanced coordination of care after discharge.

Alpesh Amin, MD, MBA, SFHM, professor and chair of the department of medicine and executive director of the hospitalist program at the University of California at Irvine, says the findings are important, but he adds that the core quality measures studied were never designed to address readmissions.

“The challenge is to find a way to connect the dots between the core measures and readmissions,” he says.

Learn more about the four "core" heart failure quality measures for hospitals by visiting the Resource Rooms on the SHM website, or check out this 80-page implementation guide, “Improving Heart Failure Care for Hospitalized Patients [PDF],” also available on SHM’s website.

Read The Hospitalist columnist Win Whitcomb’s take on readmissions penalty programs.

 

BOSTON – Avatrombopag, an investigational thrombopoietin receptor agonist, may reduce procedure-related bleeding risk in patients with chronic liver disease and thrombocytopenia, results of a phase II trial suggest.

Patients randomized to receive avatrambopag (E5501) before invasive surgical or diagnostic procedures had significantly more platelet count responses and required significantly fewer platelet transfusions than did patients randomized to placebo, Dr. Norah Terrault said at the annual meeting of the American Association for the Study of Liver Diseases.

"It was a well-tolerated drug with no dose-limiting adverse events," Dr. Terrault said, although she noted that one patient had a nonfatal episode of portal-vein thrombosis that may have been related to the drug.

Avatrombopag has been shown to mimic the effects of thrombopoietin both in vitro and in vivo, and in a phase II study it was shown to increase platelet counts in patients with chronic immune thrombocytopenia.

Dr. Terrault, associate professor of medicine in the division of gastroenterology at the University of California, San Francisco, and her colleagues tested the efficacy of short-course avatrombopag in 130 patients with chronic liver disease and thrombocytopenia prior to a planned invasive procedure. The patients were all adults with cirrhosis from viral hepatitis, nonalcoholic steatohepatitis, or alcoholic liver disease.

The trial, labeled E5501-G000-202, enrolled patients into two cohorts. In cohort A, 67 patients were randomly assigned to receive either placebo or a loading dose of a first-generation formulation of avatrombopag 100 mg on day 1, followed by a maintenance dose on days 2-7 of either 20, 40, or 80 mg daily.

In cohort B, 63 patients were randomized either to placebo or to a second-generation formulation of avatrombopag at 80 mg on day 1, followed by either 10 mg daily for days 2-7 or 20 mg/day for days 2-4 and placebo on days 5, 6, and 7.

Patients in both cohorts were scheduled for procedures 1-4 days after the end of drug dosing.

The primary end point was a platelet count response – defined as a platelet count increase from baseline of at least 20 × 10⁹/L and at least one count of greater than 50 × 10⁹/L during days 4-8 from the start of treatment. In an intention-to-treat analysis, the proportion of patients achieving the primary end point was significantly higher in each cohort compared with controls.

In cohort A, the respective responses in the 20- and 80-mg groups were seen in 7 of 18 patients on the 20-mg dose (38.9%) and in 13 of 17 on the 80-mg dose (76.5%), compared with 1 of 16 (6.3%) controls (P less than .05 for both comparisons). There was no significant difference between patients given a placebo vs. a 40-mg dose, however.

In cohort B, 9 of 21 patients on the 10-mg dose (42.9%) had a platelet count response, as did 11 of 21 (52.4%) in the 20-mg group, compared with 2 of 21 on placebo (9.5%; P less than .05 for both comparisons).

The investigators also performed an exploratory analysis looking at platelet transfusion requirements for 58 of the patients in cohort B and found that 7 of 20 (35%) controls needed preprocedure platelets, compared with 1 of 19 (5.3%) each in the 10- and 20-mg avatrombopag groups (P less than .05).

In the combined cohorts, 78 of 93 (83.9%) patients assigned to the drug had treatment-emergent adverse events, compared with 28 of 37 (75.7%) assigned to placebo. There were 15 grade-3 or -4 adverse events among avatrombopag patients (16.1%), compared with 5 among controls (13.5%).

There were three severe treatment-related events, all in patients who received the active drug, and 16 serious treatment-related events among those taking avatrombopag, compared with four on placebo (17.2% vs. 10.8%).

One patient – a 55-year-old with a history of cardiovascular disease, Child-Pugh class C cirrhosis, and a MELD (Model for End-Stage Liver Disease) score of 19 – died. The death was attributed to acute respiratory failure, cardiopulmonary arrest, and metabolic acidosis.

A 61-year-old man with Child-Pugh class C disease and a MELD score of 19 but no hepatocellular carcinoma had weight gain on study day 34, which was shown on Doppler ultrasound to be portal-vein thrombus. His peak platelet count was 199 × 10⁹/L on day 17. He was successfully treated with embolization and anticoagulation therapy.

Investigators are currently planning phase III trials with avatrombopag, Dr. Terrault said.

The study was funded by Eisai, maker of avatrombopag. Dr. Terrault receives grant and research support from the company and serves in an advisory capacity.

BOSTON – Avatrombopag, an investigational thrombopoietin receptor agonist, may reduce procedure-related bleeding risk in patients with chronic liver disease and thrombocytopenia, results of a phase II trial suggest.

Patients randomized to receive avatrambopag (E5501) before invasive surgical or diagnostic procedures had significantly more platelet count responses and required significantly fewer platelet transfusions than did patients randomized to placebo, Dr. Norah Terrault said at the annual meeting of the American Association for the Study of Liver Diseases.

"It was a well-tolerated drug with no dose-limiting adverse events," Dr. Terrault said, although she noted that one patient had a nonfatal episode of portal-vein thrombosis that may have been related to the drug.

Avatrombopag has been shown to mimic the effects of thrombopoietin both in vitro and in vivo, and in a phase II study it was shown to increase platelet counts in patients with chronic immune thrombocytopenia.

Dr. Terrault, associate professor of medicine in the division of gastroenterology at the University of California, San Francisco, and her colleagues tested the efficacy of short-course avatrombopag in 130 patients with chronic liver disease and thrombocytopenia prior to a planned invasive procedure. The patients were all adults with cirrhosis from viral hepatitis, nonalcoholic steatohepatitis, or alcoholic liver disease.

The trial, labeled E5501-G000-202, enrolled patients into two cohorts. In cohort A, 67 patients were randomly assigned to receive either placebo or a loading dose of a first-generation formulation of avatrombopag 100 mg on day 1, followed by a maintenance dose on days 2-7 of either 20, 40, or 80 mg daily.

In cohort B, 63 patients were randomized either to placebo or to a second-generation formulation of avatrombopag at 80 mg on day 1, followed by either 10 mg daily for days 2-7 or 20 mg/day for days 2-4 and placebo on days 5, 6, and 7.

Patients in both cohorts were scheduled for procedures 1-4 days after the end of drug dosing.

The primary end point was a platelet count response – defined as a platelet count increase from baseline of at least 20 × 10⁹/L and at least one count of greater than 50 × 10⁹/L during days 4-8 from the start of treatment. In an intention-to-treat analysis, the proportion of patients achieving the primary end point was significantly higher in each cohort compared with controls.

In cohort A, the respective responses in the 20- and 80-mg groups were seen in 7 of 18 patients on the 20-mg dose (38.9%) and in 13 of 17 on the 80-mg dose (76.5%), compared with 1 of 16 (6.3%) controls (P less than .05 for both comparisons). There was no significant difference between patients given a placebo vs. a 40-mg dose, however.

In cohort B, 9 of 21 patients on the 10-mg dose (42.9%) had a platelet count response, as did 11 of 21 (52.4%) in the 20-mg group, compared with 2 of 21 on placebo (9.5%; P less than .05 for both comparisons).

The investigators also performed an exploratory analysis looking at platelet transfusion requirements for 58 of the patients in cohort B and found that 7 of 20 (35%) controls needed preprocedure platelets, compared with 1 of 19 (5.3%) each in the 10- and 20-mg avatrombopag groups (P less than .05).

In the combined cohorts, 78 of 93 (83.9%) patients assigned to the drug had treatment-emergent adverse events, compared with 28 of 37 (75.7%) assigned to placebo. There were 15 grade-3 or -4 adverse events among avatrombopag patients (16.1%), compared with 5 among controls (13.5%).

There were three severe treatment-related events, all in patients who received the active drug, and 16 serious treatment-related events among those taking avatrombopag, compared with four on placebo (17.2% vs. 10.8%).

One patient – a 55-year-old with a history of cardiovascular disease, Child-Pugh class C cirrhosis, and a MELD (Model for End-Stage Liver Disease) score of 19 – died. The death was attributed to acute respiratory failure, cardiopulmonary arrest, and metabolic acidosis.

A 61-year-old man with Child-Pugh class C disease and a MELD score of 19 but no hepatocellular carcinoma had weight gain on study day 34, which was shown on Doppler ultrasound to be portal-vein thrombus. His peak platelet count was 199 × 10⁹/L on day 17. He was successfully treated with embolization and anticoagulation therapy.

Investigators are currently planning phase III trials with avatrombopag, Dr. Terrault said.

The study was funded by Eisai, maker of avatrombopag. Dr. Terrault receives grant and research support from the company and serves in an advisory capacity.

BOSTON – Avatrombopag, an investigational thrombopoietin receptor agonist, may reduce procedure-related bleeding risk in patients with chronic liver disease and thrombocytopenia, results of a phase II trial suggest.

Patients randomized to receive avatrambopag (E5501) before invasive surgical or diagnostic procedures had significantly more platelet count responses and required significantly fewer platelet transfusions than did patients randomized to placebo, Dr. Norah Terrault said at the annual meeting of the American Association for the Study of Liver Diseases.

"It was a well-tolerated drug with no dose-limiting adverse events," Dr. Terrault said, although she noted that one patient had a nonfatal episode of portal-vein thrombosis that may have been related to the drug.

Avatrombopag has been shown to mimic the effects of thrombopoietin both in vitro and in vivo, and in a phase II study it was shown to increase platelet counts in patients with chronic immune thrombocytopenia.

Dr. Terrault, associate professor of medicine in the division of gastroenterology at the University of California, San Francisco, and her colleagues tested the efficacy of short-course avatrombopag in 130 patients with chronic liver disease and thrombocytopenia prior to a planned invasive procedure. The patients were all adults with cirrhosis from viral hepatitis, nonalcoholic steatohepatitis, or alcoholic liver disease.

The trial, labeled E5501-G000-202, enrolled patients into two cohorts. In cohort A, 67 patients were randomly assigned to receive either placebo or a loading dose of a first-generation formulation of avatrombopag 100 mg on day 1, followed by a maintenance dose on days 2-7 of either 20, 40, or 80 mg daily.

In cohort B, 63 patients were randomized either to placebo or to a second-generation formulation of avatrombopag at 80 mg on day 1, followed by either 10 mg daily for days 2-7 or 20 mg/day for days 2-4 and placebo on days 5, 6, and 7.

Patients in both cohorts were scheduled for procedures 1-4 days after the end of drug dosing.

The primary end point was a platelet count response – defined as a platelet count increase from baseline of at least 20 × 10⁹/L and at least one count of greater than 50 × 10⁹/L during days 4-8 from the start of treatment. In an intention-to-treat analysis, the proportion of patients achieving the primary end point was significantly higher in each cohort compared with controls.

In cohort A, the respective responses in the 20- and 80-mg groups were seen in 7 of 18 patients on the 20-mg dose (38.9%) and in 13 of 17 on the 80-mg dose (76.5%), compared with 1 of 16 (6.3%) controls (P less than .05 for both comparisons). There was no significant difference between patients given a placebo vs. a 40-mg dose, however.

In cohort B, 9 of 21 patients on the 10-mg dose (42.9%) had a platelet count response, as did 11 of 21 (52.4%) in the 20-mg group, compared with 2 of 21 on placebo (9.5%; P less than .05 for both comparisons).

The investigators also performed an exploratory analysis looking at platelet transfusion requirements for 58 of the patients in cohort B and found that 7 of 20 (35%) controls needed preprocedure platelets, compared with 1 of 19 (5.3%) each in the 10- and 20-mg avatrombopag groups (P less than .05).

In the combined cohorts, 78 of 93 (83.9%) patients assigned to the drug had treatment-emergent adverse events, compared with 28 of 37 (75.7%) assigned to placebo. There were 15 grade-3 or -4 adverse events among avatrombopag patients (16.1%), compared with 5 among controls (13.5%).

There were three severe treatment-related events, all in patients who received the active drug, and 16 serious treatment-related events among those taking avatrombopag, compared with four on placebo (17.2% vs. 10.8%).

One patient – a 55-year-old with a history of cardiovascular disease, Child-Pugh class C cirrhosis, and a MELD (Model for End-Stage Liver Disease) score of 19 – died. The death was attributed to acute respiratory failure, cardiopulmonary arrest, and metabolic acidosis.

A 61-year-old man with Child-Pugh class C disease and a MELD score of 19 but no hepatocellular carcinoma had weight gain on study day 34, which was shown on Doppler ultrasound to be portal-vein thrombus. His peak platelet count was 199 × 10⁹/L on day 17. He was successfully treated with embolization and anticoagulation therapy.

Investigators are currently planning phase III trials with avatrombopag, Dr. Terrault said.

The study was funded by Eisai, maker of avatrombopag. Dr. Terrault receives grant and research support from the company and serves in an advisory capacity.

BOSTON  – In patients who had chronic hepatitis B infections and documented lamivudine resistance, tenofovir with or without emtricitabine produced high rates of viral suppression with no detectable resistance over 2 years.

In a phase IIIb randomized study, 89% of lamivudine-resistant patients with HBV who were randomly assigned to receive tenofovir (Viread) alone met the primary end point of HBV DNA below 400 copies/mL, compared with 86% of those assigned to a tenofovir/emtricitabine (Emtriva) combination, in an intention-to-treat analysis, Dr. Scott Fung, assistant professor of hepatology at the University of Toronto, reported at the annual meeting of the American Association for the Study of Liver Diseases.

©CDC/ Dr. Erskine Palmer

"Tenofovir monotherapy was just as safe and effective as combination therapy, suggesting that monotherapy alone was sufficient for treatment of hepatitis B," Dr. Fung said.

In addition to the high rate of viral resistance, tenofovir was associated with normalization of ALT levels in a majority of patients, and with no emergent viral resistance, he said.

The investigators enrolled 280 patients who carried virus with lamivudine-resistant mutations, were viremic (HBV DNA greater than 10³/IU per mL), and were still on lamivudine until the day of randomization. Current or prior treatment with adefovir (Hepsera) was allowed as long as the patient had received less than 48 total weeks of therapy.

A total of 133 patients who were assigned to receive tenofovir 300 mg daily completed 96 weeks of treatment and were thus available for analysis, as were 125 of those assigned to emtricitabine/tenofovir in a fixed-dose combination.

As noted before, the rates of HBV DNA below 400 copies/mL were 89% for the monotherapy arm and 86% for the combination in an analysis that considered missing data as treatment failure. When missing data were excluded from an on-treatment analysis, however, the respective rates were 96% and 95%.

Using a lower cutoff point, less than 169 copies/mL, the respective rates at 96 weeks were 86% and 84%.

In all, 70% of patients in each group had normal ALT levels at 96 weeks, and among patients with abnormally high levels at baseline nearly two-thirds in each group had normalization of ALT during the study.

The HBV e-antigen loss rate was modest, at 15% of patients on tenofovir alone and 13% on the combination. HBeAg seroconversion occurred in 11% and 10%, respectively.

Among 18 patients who qualified for genotypic resistance testing at their last on-treatment visit, there were no viral isolates demonstrating tenofovir resistance, Dr. Fung said.

There were three deaths during the study: one from gastrointestinal hemorrhage in a patient in the monotherapy group and two – one from cardiac arrest and sepsis in a patient with hepatocellular carcinoma and one from bronchopneumonia – in the combination group. The deaths were judged to be unrelated to study treatment.

There was only one serious treatment-related adverse event, occurring in the combination group (the event was unspecified), and only three patients discontinued because of adverse events – one in the monotherapy arm and two in the combination group. Five patients on tenofovir alone and four on the combination had creatinine clearance less than 50 mL/min at study end; these patients all had low baseline creatinine clearance levels, ranging from 41 to 69 mL/min, Dr. Fung noted.

The authors also looked at bone mineral density levels at baseline and at study end in 239 patients for who dual-energy x-ray absorptiometry data were available. At baseline, 33% of patients were determined to have osteopenia and 7% to have osteoporosis on spine scans and 22% and 1.3%, respectively, on hip scans. Repeat scans at 96 weeks showed that the majority of patients had a reduction in bone mineral density of about 22%, a decline that was considered not clinically significant, he said.

The study was funded by Gilead Sciences. Dr. Fung disclosed receiving grant/research support and speaking/teaching fees from the company.

BOSTON  – In patients who had chronic hepatitis B infections and documented lamivudine resistance, tenofovir with or without emtricitabine produced high rates of viral suppression with no detectable resistance over 2 years.

In a phase IIIb randomized study, 89% of lamivudine-resistant patients with HBV who were randomly assigned to receive tenofovir (Viread) alone met the primary end point of HBV DNA below 400 copies/mL, compared with 86% of those assigned to a tenofovir/emtricitabine (Emtriva) combination, in an intention-to-treat analysis, Dr. Scott Fung, assistant professor of hepatology at the University of Toronto, reported at the annual meeting of the American Association for the Study of Liver Diseases.

©CDC/ Dr. Erskine Palmer

"Tenofovir monotherapy was just as safe and effective as combination therapy, suggesting that monotherapy alone was sufficient for treatment of hepatitis B," Dr. Fung said.

In addition to the high rate of viral resistance, tenofovir was associated with normalization of ALT levels in a majority of patients, and with no emergent viral resistance, he said.

The investigators enrolled 280 patients who carried virus with lamivudine-resistant mutations, were viremic (HBV DNA greater than 10³/IU per mL), and were still on lamivudine until the day of randomization. Current or prior treatment with adefovir (Hepsera) was allowed as long as the patient had received less than 48 total weeks of therapy.

A total of 133 patients who were assigned to receive tenofovir 300 mg daily completed 96 weeks of treatment and were thus available for analysis, as were 125 of those assigned to emtricitabine/tenofovir in a fixed-dose combination.

As noted before, the rates of HBV DNA below 400 copies/mL were 89% for the monotherapy arm and 86% for the combination in an analysis that considered missing data as treatment failure. When missing data were excluded from an on-treatment analysis, however, the respective rates were 96% and 95%.

Using a lower cutoff point, less than 169 copies/mL, the respective rates at 96 weeks were 86% and 84%.

In all, 70% of patients in each group had normal ALT levels at 96 weeks, and among patients with abnormally high levels at baseline nearly two-thirds in each group had normalization of ALT during the study.

The HBV e-antigen loss rate was modest, at 15% of patients on tenofovir alone and 13% on the combination. HBeAg seroconversion occurred in 11% and 10%, respectively.

Among 18 patients who qualified for genotypic resistance testing at their last on-treatment visit, there were no viral isolates demonstrating tenofovir resistance, Dr. Fung said.

There were three deaths during the study: one from gastrointestinal hemorrhage in a patient in the monotherapy group and two – one from cardiac arrest and sepsis in a patient with hepatocellular carcinoma and one from bronchopneumonia – in the combination group. The deaths were judged to be unrelated to study treatment.

There was only one serious treatment-related adverse event, occurring in the combination group (the event was unspecified), and only three patients discontinued because of adverse events – one in the monotherapy arm and two in the combination group. Five patients on tenofovir alone and four on the combination had creatinine clearance less than 50 mL/min at study end; these patients all had low baseline creatinine clearance levels, ranging from 41 to 69 mL/min, Dr. Fung noted.

The authors also looked at bone mineral density levels at baseline and at study end in 239 patients for who dual-energy x-ray absorptiometry data were available. At baseline, 33% of patients were determined to have osteopenia and 7% to have osteoporosis on spine scans and 22% and 1.3%, respectively, on hip scans. Repeat scans at 96 weeks showed that the majority of patients had a reduction in bone mineral density of about 22%, a decline that was considered not clinically significant, he said.

The study was funded by Gilead Sciences. Dr. Fung disclosed receiving grant/research support and speaking/teaching fees from the company.

BOSTON  – In patients who had chronic hepatitis B infections and documented lamivudine resistance, tenofovir with or without emtricitabine produced high rates of viral suppression with no detectable resistance over 2 years.

In a phase IIIb randomized study, 89% of lamivudine-resistant patients with HBV who were randomly assigned to receive tenofovir (Viread) alone met the primary end point of HBV DNA below 400 copies/mL, compared with 86% of those assigned to a tenofovir/emtricitabine (Emtriva) combination, in an intention-to-treat analysis, Dr. Scott Fung, assistant professor of hepatology at the University of Toronto, reported at the annual meeting of the American Association for the Study of Liver Diseases.

©CDC/ Dr. Erskine Palmer

"Tenofovir monotherapy was just as safe and effective as combination therapy, suggesting that monotherapy alone was sufficient for treatment of hepatitis B," Dr. Fung said.

In addition to the high rate of viral resistance, tenofovir was associated with normalization of ALT levels in a majority of patients, and with no emergent viral resistance, he said.

The investigators enrolled 280 patients who carried virus with lamivudine-resistant mutations, were viremic (HBV DNA greater than 10³/IU per mL), and were still on lamivudine until the day of randomization. Current or prior treatment with adefovir (Hepsera) was allowed as long as the patient had received less than 48 total weeks of therapy.

A total of 133 patients who were assigned to receive tenofovir 300 mg daily completed 96 weeks of treatment and were thus available for analysis, as were 125 of those assigned to emtricitabine/tenofovir in a fixed-dose combination.

As noted before, the rates of HBV DNA below 400 copies/mL were 89% for the monotherapy arm and 86% for the combination in an analysis that considered missing data as treatment failure. When missing data were excluded from an on-treatment analysis, however, the respective rates were 96% and 95%.

Using a lower cutoff point, less than 169 copies/mL, the respective rates at 96 weeks were 86% and 84%.

In all, 70% of patients in each group had normal ALT levels at 96 weeks, and among patients with abnormally high levels at baseline nearly two-thirds in each group had normalization of ALT during the study.

The HBV e-antigen loss rate was modest, at 15% of patients on tenofovir alone and 13% on the combination. HBeAg seroconversion occurred in 11% and 10%, respectively.

Among 18 patients who qualified for genotypic resistance testing at their last on-treatment visit, there were no viral isolates demonstrating tenofovir resistance, Dr. Fung said.

There were three deaths during the study: one from gastrointestinal hemorrhage in a patient in the monotherapy group and two – one from cardiac arrest and sepsis in a patient with hepatocellular carcinoma and one from bronchopneumonia – in the combination group. The deaths were judged to be unrelated to study treatment.

There was only one serious treatment-related adverse event, occurring in the combination group (the event was unspecified), and only three patients discontinued because of adverse events – one in the monotherapy arm and two in the combination group. Five patients on tenofovir alone and four on the combination had creatinine clearance less than 50 mL/min at study end; these patients all had low baseline creatinine clearance levels, ranging from 41 to 69 mL/min, Dr. Fung noted.

The authors also looked at bone mineral density levels at baseline and at study end in 239 patients for who dual-energy x-ray absorptiometry data were available. At baseline, 33% of patients were determined to have osteopenia and 7% to have osteoporosis on spine scans and 22% and 1.3%, respectively, on hip scans. Repeat scans at 96 weeks showed that the majority of patients had a reduction in bone mineral density of about 22%, a decline that was considered not clinically significant, he said.

The study was funded by Gilead Sciences. Dr. Fung disclosed receiving grant/research support and speaking/teaching fees from the company.