Heidi Splete

ORLANDO – Patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia who took 400 mg of nilotinib twice daily had an overall survival rate of 97% after 3 years, investigators reported Dec. 6 at the annual meeting of the American Society of Hematology.

Nilotinib was approved by the Food and Drug Administration in June 2010 as a first-line therapy for newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase after the drug demonstrated higher and faster molecular response rates than imatinib. The current study was conducted by Dr. Gianantonio Rosti of the University of Bologna (Italy) and associates to confirm that the efficacy of nilotinib is durable over a 3-year period, the time during which most failures on imatinib occur.

The investigators enrolled 73 patients with newly diagnosed Ph+ CML in a phase II open-label, multicenter clinical trial. The patients ranged in age from 18 to 83 years, with a median age of 51 years. All patients received 400 mg of nilotinib two times per day, Dr. Rosti said at a press briefing in advance of his presentation at the meeting.

The study’s primary end point was a complete cytogenetic response rate at 12 months, meaning that no cells containing a Philadelphia chromosome were found in the patient’s bone marrow. The complete cytogenetic response rate was 78% at 3 months and 96% at 6, 12, and 18 months. Within 12 months, all patients had achieved a complete cytogenetic response at least once.

The progression-free survival and failure-free survival rates were 97% after 3 years, and the event-free survival rate was 91% after a median follow-up of 36 months.

The study is ongoing, and the current median follow-up time is longer than 3 years (30-40 months), Dr. Rosti said. Patient responses remained stable, and only one patient progressed to alternative lengthening of telomeres–-associated promyelocytic leukemia, Dr. Rosti said. A total of 97% of patients obtained a major molecular response. In addition, 70% obtained a complete molecular response, and 25% of these patients are stable, he said.

Dr. Rosti said he has received research funding from Novartis. He has also served as a consultant and on the speakers bureau and board of directors or advisory committee for the company. He has received honoraria and served on the speakers bureau for Bristol-Myers Squibb, and on the speakers bureau for Roche.

ORLANDO – Patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia who took 400 mg of nilotinib twice daily had an overall survival rate of 97% after 3 years, investigators reported Dec. 6 at the annual meeting of the American Society of Hematology.

Nilotinib was approved by the Food and Drug Administration in June 2010 as a first-line therapy for newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase after the drug demonstrated higher and faster molecular response rates than imatinib. The current study was conducted by Dr. Gianantonio Rosti of the University of Bologna (Italy) and associates to confirm that the efficacy of nilotinib is durable over a 3-year period, the time during which most failures on imatinib occur.

The investigators enrolled 73 patients with newly diagnosed Ph+ CML in a phase II open-label, multicenter clinical trial. The patients ranged in age from 18 to 83 years, with a median age of 51 years. All patients received 400 mg of nilotinib two times per day, Dr. Rosti said at a press briefing in advance of his presentation at the meeting.

The study’s primary end point was a complete cytogenetic response rate at 12 months, meaning that no cells containing a Philadelphia chromosome were found in the patient’s bone marrow. The complete cytogenetic response rate was 78% at 3 months and 96% at 6, 12, and 18 months. Within 12 months, all patients had achieved a complete cytogenetic response at least once.

The progression-free survival and failure-free survival rates were 97% after 3 years, and the event-free survival rate was 91% after a median follow-up of 36 months.

The study is ongoing, and the current median follow-up time is longer than 3 years (30-40 months), Dr. Rosti said. Patient responses remained stable, and only one patient progressed to alternative lengthening of telomeres–-associated promyelocytic leukemia, Dr. Rosti said. A total of 97% of patients obtained a major molecular response. In addition, 70% obtained a complete molecular response, and 25% of these patients are stable, he said.

Dr. Rosti said he has received research funding from Novartis. He has also served as a consultant and on the speakers bureau and board of directors or advisory committee for the company. He has received honoraria and served on the speakers bureau for Bristol-Myers Squibb, and on the speakers bureau for Roche.

ORLANDO – Patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia who took 400 mg of nilotinib twice daily had an overall survival rate of 97% after 3 years, investigators reported Dec. 6 at the annual meeting of the American Society of Hematology.

Nilotinib was approved by the Food and Drug Administration in June 2010 as a first-line therapy for newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase after the drug demonstrated higher and faster molecular response rates than imatinib. The current study was conducted by Dr. Gianantonio Rosti of the University of Bologna (Italy) and associates to confirm that the efficacy of nilotinib is durable over a 3-year period, the time during which most failures on imatinib occur.

The investigators enrolled 73 patients with newly diagnosed Ph+ CML in a phase II open-label, multicenter clinical trial. The patients ranged in age from 18 to 83 years, with a median age of 51 years. All patients received 400 mg of nilotinib two times per day, Dr. Rosti said at a press briefing in advance of his presentation at the meeting.

The study’s primary end point was a complete cytogenetic response rate at 12 months, meaning that no cells containing a Philadelphia chromosome were found in the patient’s bone marrow. The complete cytogenetic response rate was 78% at 3 months and 96% at 6, 12, and 18 months. Within 12 months, all patients had achieved a complete cytogenetic response at least once.

The progression-free survival and failure-free survival rates were 97% after 3 years, and the event-free survival rate was 91% after a median follow-up of 36 months.

The study is ongoing, and the current median follow-up time is longer than 3 years (30-40 months), Dr. Rosti said. Patient responses remained stable, and only one patient progressed to alternative lengthening of telomeres–-associated promyelocytic leukemia, Dr. Rosti said. A total of 97% of patients obtained a major molecular response. In addition, 70% obtained a complete molecular response, and 25% of these patients are stable, he said.

Dr. Rosti said he has received research funding from Novartis. He has also served as a consultant and on the speakers bureau and board of directors or advisory committee for the company. He has received honoraria and served on the speakers bureau for Bristol-Myers Squibb, and on the speakers bureau for Roche.

ORLANDO – Brentuximab vedotin, an investigational agent, was associated with complete remission in 34% of patients whose Hodgkin’s lymphoma recurred after autologous stem cell transplantation, according to the results of a phase II trial involving 102 patients.

"The antibody component of the drug allows for the selective delivery of the chemotherapeutic agent directly into the Hodgkin’s lymphoma cells," Dr. Robert Chen said at a press conference held in conjunction with the annual meeting of the American Society of Hematology.

"The overall response rate was 75%," with a median duration of 29 weeks, said Dr. Chen of City of Hope National Medical Center in Duarte, Calif. "Overall, 94% of the patients achieved any kind of tumor reduction," he said.

Dr. Chen and colleagues conducted the single-arm, multicenter study to evaluate the safety and efficacy of brentuximab vedotin, an antibody-drug conjugate, in patients with relapsed or refractory Hodgkin’s lymphoma following autologous stem cell transplants. In general, the prognosis for this patient population is poor, with a median survival time of 2.4 years, Dr. Chen noted.

The patients received 1.8 mg/kg of brentuximab vedotin every 3 weeks in the form of a 30-minute intravenous infusion. Patients had up to 16 treatment cycles.

The most common side effect was peripheral neuropathy, reported by 43% of the patients. However, approximately two-thirds of these patients had resolution of the peripheral neuropathy after treatment completion. The side effect profile is manageable, compared with other combination chemotherapy regimens, Dr. Chen said. Other commonly reported side effects included fatigue, nausea, and upper respiratory tract infections.

The patients ranged in age from 15 to 77 years, with a median age of 31 years, and 53% were women. The patients had received an average of 3.5 previous chemotherapy treatments in addition to autologous stem cell transplantation. The average length of treatment was 27 weeks (nine cycles), and patients were followed every 12 weeks.

A total of 96 of 102 patients (94%) achieved some degree of tumor reduction, and the estimated 12-month overall survival was 88%.

The results of this phase II study will be submitted to the Food and Drug Administration early in 2011, Dr. Chen said. Two additional trials are underway to evaluate brentuximab vedotin’s effectiveness in newly diagnosed Hodgkin’s lymphoma patients and as maintenance therapy.

"Once a patient fails a transplant, the prognosis is generally poor, said Dr. Ginna G. Laport, an associate professor of medicine at Stanford (Calif.) University. Dr. Laport served as the press conference moderator and several of her patients participated in the study. Brentuximab vedotin represents "a big breakthrough for this population," she said. "I think this is a very exciting drug."

Dr. Chen and his colleagues received research funding from the study sponsor, Seattle Genetics.

ORLANDO – Brentuximab vedotin, an investigational agent, was associated with complete remission in 34% of patients whose Hodgkin’s lymphoma recurred after autologous stem cell transplantation, according to the results of a phase II trial involving 102 patients.

"The antibody component of the drug allows for the selective delivery of the chemotherapeutic agent directly into the Hodgkin’s lymphoma cells," Dr. Robert Chen said at a press conference held in conjunction with the annual meeting of the American Society of Hematology.

"The overall response rate was 75%," with a median duration of 29 weeks, said Dr. Chen of City of Hope National Medical Center in Duarte, Calif. "Overall, 94% of the patients achieved any kind of tumor reduction," he said.

Dr. Chen and colleagues conducted the single-arm, multicenter study to evaluate the safety and efficacy of brentuximab vedotin, an antibody-drug conjugate, in patients with relapsed or refractory Hodgkin’s lymphoma following autologous stem cell transplants. In general, the prognosis for this patient population is poor, with a median survival time of 2.4 years, Dr. Chen noted.

The patients received 1.8 mg/kg of brentuximab vedotin every 3 weeks in the form of a 30-minute intravenous infusion. Patients had up to 16 treatment cycles.

The most common side effect was peripheral neuropathy, reported by 43% of the patients. However, approximately two-thirds of these patients had resolution of the peripheral neuropathy after treatment completion. The side effect profile is manageable, compared with other combination chemotherapy regimens, Dr. Chen said. Other commonly reported side effects included fatigue, nausea, and upper respiratory tract infections.

The patients ranged in age from 15 to 77 years, with a median age of 31 years, and 53% were women. The patients had received an average of 3.5 previous chemotherapy treatments in addition to autologous stem cell transplantation. The average length of treatment was 27 weeks (nine cycles), and patients were followed every 12 weeks.

A total of 96 of 102 patients (94%) achieved some degree of tumor reduction, and the estimated 12-month overall survival was 88%.

The results of this phase II study will be submitted to the Food and Drug Administration early in 2011, Dr. Chen said. Two additional trials are underway to evaluate brentuximab vedotin’s effectiveness in newly diagnosed Hodgkin’s lymphoma patients and as maintenance therapy.

"Once a patient fails a transplant, the prognosis is generally poor, said Dr. Ginna G. Laport, an associate professor of medicine at Stanford (Calif.) University. Dr. Laport served as the press conference moderator and several of her patients participated in the study. Brentuximab vedotin represents "a big breakthrough for this population," she said. "I think this is a very exciting drug."

Dr. Chen and his colleagues received research funding from the study sponsor, Seattle Genetics.

ORLANDO – Brentuximab vedotin, an investigational agent, was associated with complete remission in 34% of patients whose Hodgkin’s lymphoma recurred after autologous stem cell transplantation, according to the results of a phase II trial involving 102 patients.

"The antibody component of the drug allows for the selective delivery of the chemotherapeutic agent directly into the Hodgkin’s lymphoma cells," Dr. Robert Chen said at a press conference held in conjunction with the annual meeting of the American Society of Hematology.

"The overall response rate was 75%," with a median duration of 29 weeks, said Dr. Chen of City of Hope National Medical Center in Duarte, Calif. "Overall, 94% of the patients achieved any kind of tumor reduction," he said.

Dr. Chen and colleagues conducted the single-arm, multicenter study to evaluate the safety and efficacy of brentuximab vedotin, an antibody-drug conjugate, in patients with relapsed or refractory Hodgkin’s lymphoma following autologous stem cell transplants. In general, the prognosis for this patient population is poor, with a median survival time of 2.4 years, Dr. Chen noted.

The patients received 1.8 mg/kg of brentuximab vedotin every 3 weeks in the form of a 30-minute intravenous infusion. Patients had up to 16 treatment cycles.

The most common side effect was peripheral neuropathy, reported by 43% of the patients. However, approximately two-thirds of these patients had resolution of the peripheral neuropathy after treatment completion. The side effect profile is manageable, compared with other combination chemotherapy regimens, Dr. Chen said. Other commonly reported side effects included fatigue, nausea, and upper respiratory tract infections.

The patients ranged in age from 15 to 77 years, with a median age of 31 years, and 53% were women. The patients had received an average of 3.5 previous chemotherapy treatments in addition to autologous stem cell transplantation. The average length of treatment was 27 weeks (nine cycles), and patients were followed every 12 weeks.

A total of 96 of 102 patients (94%) achieved some degree of tumor reduction, and the estimated 12-month overall survival was 88%.

The results of this phase II study will be submitted to the Food and Drug Administration early in 2011, Dr. Chen said. Two additional trials are underway to evaluate brentuximab vedotin’s effectiveness in newly diagnosed Hodgkin’s lymphoma patients and as maintenance therapy.

"Once a patient fails a transplant, the prognosis is generally poor, said Dr. Ginna G. Laport, an associate professor of medicine at Stanford (Calif.) University. Dr. Laport served as the press conference moderator and several of her patients participated in the study. Brentuximab vedotin represents "a big breakthrough for this population," she said. "I think this is a very exciting drug."

Dr. Chen and his colleagues received research funding from the study sponsor, Seattle Genetics.

ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.

Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.

Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).

The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.

Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.

Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.

Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.

Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).

The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.

Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.

Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.

Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.

Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).

The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.

Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.

Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.

Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.

Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).

The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.

Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.

Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.

Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.

Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).

The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.

Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.

Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.

Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.

Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).

The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.

Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.

Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

ATLANTA – Use of tumor necrosis factor inhibitors reduced the risk of developing type 2 diabetes by 60%, based on data from 1,287 nondiabetic adults with rheumatoid arthritis. The results were presented at the annual scientific meeting of the American Academy of Rheumatology.

"Interventions that treat RA and improve insulin resistance are highly desirable," said Dr. Jana Antohe of Geisinger Health System in Danville, Pa.

To examine the impact of TNF inhibitor use in RA patients, Dr. Antohe and her colleagues followed 1,287 incident RA patients who were identified during January 2001-March 2008 at a rural tertiary health center. Of the 1,539 RA patients identified, 252 with preexisting diabetes were excluded.

The researchers compared the 884 patients who had never used TNF inhibitors with the 403 patients who had ever used them. Patients in the ever-use group had a higher median body mass index and C-reactive protein (CRP) level than did the never-use group, but these differences were not significant.

After a median follow-up time of 35 months for the ever users and 23 months for the never users, the researchers identified 13 new cases of diabetes in the ever-use group and 43 in the never-use group, for incidence rates of 11/1,000 person-years and 22/1,000 person-years, respectively.

The median age of the patients was 61 years, the median BMI was 28.6 kg/m2, 63% were women, and 97% were white. The findings were adjusted for gender, age, race, hypertension, BMI, positive rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) levels, erythrocyte sedimentation rate, CRP levels, and the use of NSAIDs, glucocorticoids, hydroxychloroquine, and methotrexate.

Additional research is needed to confirm the findings in patients at increased risk for cardiovascular disease, Dr. Antohe said.

Dr. Antohe said that she had no financial conflicts to disclose. Several of her co-investigators have received research grants from pharmaceutical companies including Wyeth, Amgen, and Centocor.

ATLANTA – Use of tumor necrosis factor inhibitors reduced the risk of developing type 2 diabetes by 60%, based on data from 1,287 nondiabetic adults with rheumatoid arthritis. The results were presented at the annual scientific meeting of the American Academy of Rheumatology.

"Interventions that treat RA and improve insulin resistance are highly desirable," said Dr. Jana Antohe of Geisinger Health System in Danville, Pa.

To examine the impact of TNF inhibitor use in RA patients, Dr. Antohe and her colleagues followed 1,287 incident RA patients who were identified during January 2001-March 2008 at a rural tertiary health center. Of the 1,539 RA patients identified, 252 with preexisting diabetes were excluded.

The researchers compared the 884 patients who had never used TNF inhibitors with the 403 patients who had ever used them. Patients in the ever-use group had a higher median body mass index and C-reactive protein (CRP) level than did the never-use group, but these differences were not significant.

After a median follow-up time of 35 months for the ever users and 23 months for the never users, the researchers identified 13 new cases of diabetes in the ever-use group and 43 in the never-use group, for incidence rates of 11/1,000 person-years and 22/1,000 person-years, respectively.

The median age of the patients was 61 years, the median BMI was 28.6 kg/m2, 63% were women, and 97% were white. The findings were adjusted for gender, age, race, hypertension, BMI, positive rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) levels, erythrocyte sedimentation rate, CRP levels, and the use of NSAIDs, glucocorticoids, hydroxychloroquine, and methotrexate.

Additional research is needed to confirm the findings in patients at increased risk for cardiovascular disease, Dr. Antohe said.

Dr. Antohe said that she had no financial conflicts to disclose. Several of her co-investigators have received research grants from pharmaceutical companies including Wyeth, Amgen, and Centocor.

ATLANTA – Use of tumor necrosis factor inhibitors reduced the risk of developing type 2 diabetes by 60%, based on data from 1,287 nondiabetic adults with rheumatoid arthritis. The results were presented at the annual scientific meeting of the American Academy of Rheumatology.

"Interventions that treat RA and improve insulin resistance are highly desirable," said Dr. Jana Antohe of Geisinger Health System in Danville, Pa.

To examine the impact of TNF inhibitor use in RA patients, Dr. Antohe and her colleagues followed 1,287 incident RA patients who were identified during January 2001-March 2008 at a rural tertiary health center. Of the 1,539 RA patients identified, 252 with preexisting diabetes were excluded.

The researchers compared the 884 patients who had never used TNF inhibitors with the 403 patients who had ever used them. Patients in the ever-use group had a higher median body mass index and C-reactive protein (CRP) level than did the never-use group, but these differences were not significant.

After a median follow-up time of 35 months for the ever users and 23 months for the never users, the researchers identified 13 new cases of diabetes in the ever-use group and 43 in the never-use group, for incidence rates of 11/1,000 person-years and 22/1,000 person-years, respectively.

The median age of the patients was 61 years, the median BMI was 28.6 kg/m2, 63% were women, and 97% were white. The findings were adjusted for gender, age, race, hypertension, BMI, positive rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) levels, erythrocyte sedimentation rate, CRP levels, and the use of NSAIDs, glucocorticoids, hydroxychloroquine, and methotrexate.

Additional research is needed to confirm the findings in patients at increased risk for cardiovascular disease, Dr. Antohe said.

Dr. Antohe said that she had no financial conflicts to disclose. Several of her co-investigators have received research grants from pharmaceutical companies including Wyeth, Amgen, and Centocor.

WASHINGTON — Daily doses of 600 international units of vitamin D and between 700 and 1,300 mg of calcium are enough for most children and adults in the United States and Canada, according to a report on new dietary reference intakes issued by the Institute of Medicine.

These new dietary reference intakes for calcium and vitamin D should provide “greater assurance that widespread vitamin D deficiency is not a public health problem,” Dr. Steven Clinton, a member of the IOM committee that issued the report at a press briefing.

After reviewing national databases on blood levels from the United States and Canada, the committee determined that most people in both countries are currently meeting their needs for vitamin D. Adequate vitamin D was defined as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Dr. Clinton, a medical oncologist at Ohio State University, Columbus, predicted that physicians will become more comfortable using recommended dietary allowances to advise patients about calcium and vitamin D intake and noted that vitamin D screening “probably should not be part of routine medical care.”

The IOM reviewers examined approximately 1,000 published studies and scientific testimonies to determine the levels of calcium and vitamin D needed to maintain health.

Based on their findings, 700 mg/day of calcium is enough for most children aged 1-3 years, and 1,000 mg is appropriate for most children aged 4-8 years. Older children and teens aged 9-18 years need no more than 1,300 mg/day, and most adults aged 19-50 years and men through 71 years need no more than 1,000 mg daily. For women aged 51 years and older and men aged 71 years and older, 1,200 mg of calcium per day is recommended, but more than that is unnecessary, according to the report.

As for vitamin D, the IOM report states that 600 IU/day meets the needs of almost all children and adults aged 1 year through 70 years, including pregnant and lactating women. For men and women aged 71 years and older, the RDA increases to 800 IU/day to accommodate age-related physical and behavioral changes.

The report lists an upper level for daily vitamin D intake of 1,000 IU for infants up to 6 months of age and 1,500 IU for infants aged 6 months to 12 months. The upper levels for children aged 1-3 years and 4-8 years are 2,500 IU and 3,000 IU, respectively. For all other life stages, the upper level is 4,000 IU.

“What we have concluded may be surprising to some,” Dr. Ross said. “I was surprised to find that vitamin D requirements don't vary much by age.”

The new recommendation came not a moment too soon, said Dr. Russell Chesney, professor and chairman of pediatrics at the University of Tennessee Health Science Center in Memphis, at the annual meeting of the American Academy of Pediatrics in San Francisco.

Dr. Chesney, who cited a long list of potential health benefits for the substance. “Vitamin D truly is the center of the universe,” he joked.

Among the conditions that vitamin D may ameliorate include infectious diseases, ovarian cancer, multiple sclerosis, rheumatoid arthritis, inflammatory bowel syndrome, wheezing, diabetes type 1 and 2, hypertension, atherosclerosis, colorectal cancer, prostate cancer, and breast cancer.

Actually, vitamin D supplementation dates back to the days when mothers spooned cod-liver oil into their children's mouths to prevent rickets. Since then, evidence has mounted for other benefits. Most claims are based on epidemiologic studies. For example, people who live at higher altitudes and get more sunshine exposure – which causes vitamin D synthesis – may suffer less from tuberculosis. “Our ancestors were right when they said we should go to sanatoriums in the mountains,” said Dr. Chesney.

He added that prospective trials are still needed. “This is suspected. This is not proven.”But a few small studies have already reinforced such findings.

In one recent study that Dr. Chesney described, a group of 167 Japanese children took supplements of 1,200 IU of vitamin D, while another group of 167 took a placebo. Those who took the vitamin D had half the influenza incidence of the placebo group, as well as fewer attacks of asthma. Other research suggests that vitamin D inhibits proinflammatory and autoimmune cytokines and promotes those that are anti-inflammatory, said Dr. Chesney.

So many claims of benefits for one vitamin might sound exaggerated, he acknowledged. But it's also true that vitamin D levels are declining in the United States as Americans spend more time indoors and take precautions to avoid skin cancer.

“This is not an advertisement for all of us to go out to the beach,” said Dr. Chesney. “But it is a point that we are not getting as much sunshine as a society as we used to, and in that case, we may need to get supplementation.”

Dr. Chesney disclosed that he serves on the board of advisors of Cytochroma.

Laird Harrison contributed to this report.

This is not an advertisement for all of us to go out to the beach. But we may need vitamin D supplementation.

Source DR. CHESNEY

WASHINGTON — Daily doses of 600 international units of vitamin D and between 700 and 1,300 mg of calcium are enough for most children and adults in the United States and Canada, according to a report on new dietary reference intakes issued by the Institute of Medicine.

These new dietary reference intakes for calcium and vitamin D should provide “greater assurance that widespread vitamin D deficiency is not a public health problem,” Dr. Steven Clinton, a member of the IOM committee that issued the report at a press briefing.

After reviewing national databases on blood levels from the United States and Canada, the committee determined that most people in both countries are currently meeting their needs for vitamin D. Adequate vitamin D was defined as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Dr. Clinton, a medical oncologist at Ohio State University, Columbus, predicted that physicians will become more comfortable using recommended dietary allowances to advise patients about calcium and vitamin D intake and noted that vitamin D screening “probably should not be part of routine medical care.”

The IOM reviewers examined approximately 1,000 published studies and scientific testimonies to determine the levels of calcium and vitamin D needed to maintain health.

Based on their findings, 700 mg/day of calcium is enough for most children aged 1-3 years, and 1,000 mg is appropriate for most children aged 4-8 years. Older children and teens aged 9-18 years need no more than 1,300 mg/day, and most adults aged 19-50 years and men through 71 years need no more than 1,000 mg daily. For women aged 51 years and older and men aged 71 years and older, 1,200 mg of calcium per day is recommended, but more than that is unnecessary, according to the report.

As for vitamin D, the IOM report states that 600 IU/day meets the needs of almost all children and adults aged 1 year through 70 years, including pregnant and lactating women. For men and women aged 71 years and older, the RDA increases to 800 IU/day to accommodate age-related physical and behavioral changes.

The report lists an upper level for daily vitamin D intake of 1,000 IU for infants up to 6 months of age and 1,500 IU for infants aged 6 months to 12 months. The upper levels for children aged 1-3 years and 4-8 years are 2,500 IU and 3,000 IU, respectively. For all other life stages, the upper level is 4,000 IU.

“What we have concluded may be surprising to some,” Dr. Ross said. “I was surprised to find that vitamin D requirements don't vary much by age.”

The new recommendation came not a moment too soon, said Dr. Russell Chesney, professor and chairman of pediatrics at the University of Tennessee Health Science Center in Memphis, at the annual meeting of the American Academy of Pediatrics in San Francisco.

Dr. Chesney, who cited a long list of potential health benefits for the substance. “Vitamin D truly is the center of the universe,” he joked.

Among the conditions that vitamin D may ameliorate include infectious diseases, ovarian cancer, multiple sclerosis, rheumatoid arthritis, inflammatory bowel syndrome, wheezing, diabetes type 1 and 2, hypertension, atherosclerosis, colorectal cancer, prostate cancer, and breast cancer.

Actually, vitamin D supplementation dates back to the days when mothers spooned cod-liver oil into their children's mouths to prevent rickets. Since then, evidence has mounted for other benefits. Most claims are based on epidemiologic studies. For example, people who live at higher altitudes and get more sunshine exposure – which causes vitamin D synthesis – may suffer less from tuberculosis. “Our ancestors were right when they said we should go to sanatoriums in the mountains,” said Dr. Chesney.

He added that prospective trials are still needed. “This is suspected. This is not proven.”But a few small studies have already reinforced such findings.

In one recent study that Dr. Chesney described, a group of 167 Japanese children took supplements of 1,200 IU of vitamin D, while another group of 167 took a placebo. Those who took the vitamin D had half the influenza incidence of the placebo group, as well as fewer attacks of asthma. Other research suggests that vitamin D inhibits proinflammatory and autoimmune cytokines and promotes those that are anti-inflammatory, said Dr. Chesney.

So many claims of benefits for one vitamin might sound exaggerated, he acknowledged. But it's also true that vitamin D levels are declining in the United States as Americans spend more time indoors and take precautions to avoid skin cancer.

“This is not an advertisement for all of us to go out to the beach,” said Dr. Chesney. “But it is a point that we are not getting as much sunshine as a society as we used to, and in that case, we may need to get supplementation.”

Dr. Chesney disclosed that he serves on the board of advisors of Cytochroma.

Laird Harrison contributed to this report.

This is not an advertisement for all of us to go out to the beach. But we may need vitamin D supplementation.

Source DR. CHESNEY

WASHINGTON — Daily doses of 600 international units of vitamin D and between 700 and 1,300 mg of calcium are enough for most children and adults in the United States and Canada, according to a report on new dietary reference intakes issued by the Institute of Medicine.

These new dietary reference intakes for calcium and vitamin D should provide “greater assurance that widespread vitamin D deficiency is not a public health problem,” Dr. Steven Clinton, a member of the IOM committee that issued the report at a press briefing.

After reviewing national databases on blood levels from the United States and Canada, the committee determined that most people in both countries are currently meeting their needs for vitamin D. Adequate vitamin D was defined as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Dr. Clinton, a medical oncologist at Ohio State University, Columbus, predicted that physicians will become more comfortable using recommended dietary allowances to advise patients about calcium and vitamin D intake and noted that vitamin D screening “probably should not be part of routine medical care.”

The IOM reviewers examined approximately 1,000 published studies and scientific testimonies to determine the levels of calcium and vitamin D needed to maintain health.

Based on their findings, 700 mg/day of calcium is enough for most children aged 1-3 years, and 1,000 mg is appropriate for most children aged 4-8 years. Older children and teens aged 9-18 years need no more than 1,300 mg/day, and most adults aged 19-50 years and men through 71 years need no more than 1,000 mg daily. For women aged 51 years and older and men aged 71 years and older, 1,200 mg of calcium per day is recommended, but more than that is unnecessary, according to the report.

As for vitamin D, the IOM report states that 600 IU/day meets the needs of almost all children and adults aged 1 year through 70 years, including pregnant and lactating women. For men and women aged 71 years and older, the RDA increases to 800 IU/day to accommodate age-related physical and behavioral changes.

The report lists an upper level for daily vitamin D intake of 1,000 IU for infants up to 6 months of age and 1,500 IU for infants aged 6 months to 12 months. The upper levels for children aged 1-3 years and 4-8 years are 2,500 IU and 3,000 IU, respectively. For all other life stages, the upper level is 4,000 IU.

“What we have concluded may be surprising to some,” Dr. Ross said. “I was surprised to find that vitamin D requirements don't vary much by age.”

The new recommendation came not a moment too soon, said Dr. Russell Chesney, professor and chairman of pediatrics at the University of Tennessee Health Science Center in Memphis, at the annual meeting of the American Academy of Pediatrics in San Francisco.

Dr. Chesney, who cited a long list of potential health benefits for the substance. “Vitamin D truly is the center of the universe,” he joked.

Among the conditions that vitamin D may ameliorate include infectious diseases, ovarian cancer, multiple sclerosis, rheumatoid arthritis, inflammatory bowel syndrome, wheezing, diabetes type 1 and 2, hypertension, atherosclerosis, colorectal cancer, prostate cancer, and breast cancer.

Actually, vitamin D supplementation dates back to the days when mothers spooned cod-liver oil into their children's mouths to prevent rickets. Since then, evidence has mounted for other benefits. Most claims are based on epidemiologic studies. For example, people who live at higher altitudes and get more sunshine exposure – which causes vitamin D synthesis – may suffer less from tuberculosis. “Our ancestors were right when they said we should go to sanatoriums in the mountains,” said Dr. Chesney.

He added that prospective trials are still needed. “This is suspected. This is not proven.”But a few small studies have already reinforced such findings.

In one recent study that Dr. Chesney described, a group of 167 Japanese children took supplements of 1,200 IU of vitamin D, while another group of 167 took a placebo. Those who took the vitamin D had half the influenza incidence of the placebo group, as well as fewer attacks of asthma. Other research suggests that vitamin D inhibits proinflammatory and autoimmune cytokines and promotes those that are anti-inflammatory, said Dr. Chesney.

So many claims of benefits for one vitamin might sound exaggerated, he acknowledged. But it's also true that vitamin D levels are declining in the United States as Americans spend more time indoors and take precautions to avoid skin cancer.

“This is not an advertisement for all of us to go out to the beach,” said Dr. Chesney. “But it is a point that we are not getting as much sunshine as a society as we used to, and in that case, we may need to get supplementation.”

Dr. Chesney disclosed that he serves on the board of advisors of Cytochroma.

Laird Harrison contributed to this report.

This is not an advertisement for all of us to go out to the beach. But we may need vitamin D supplementation.

Source DR. CHESNEY

ATLANTA — Use of tumor necrosis factor inhibitors reduced the risk of developing type 2 diabetes by 60% in a single-center study.

Dr. Jana Antohe of Geisinger Health System in Danville, Penn., and her colleagues followed 1,287 nondiabetic incident rheumatoid arthritis patients identified during January 2001–March 2008 at a rural tertiary health center.

The researchers compared the 884 patients who had never used TNF inhibitors with the 403 patients who had ever used them. Patients in the ever-use group had a higher median body mass index and C-reactive protein (CRP) level than did the never-use group, but these differences were not significant.

After a median follow-up time of 35 months for the ever users and 23 months for the never users, the researchers identified 13 new cases of diabetes in the ever-use group and 43 in the never-use group, for incidence rates of 11/1,000 and 22/1,000 person-years, respectively.

The median age of the patients was 61 years, the median BMI was 28.6 kg/m

Dr. Antohe had no financial conflicts to disclose. Several of her co-investigators have received research grants from pharmaceutical companies including Wyeth, Amgen, and Centocor.

ATLANTA — Use of tumor necrosis factor inhibitors reduced the risk of developing type 2 diabetes by 60% in a single-center study.

Dr. Jana Antohe of Geisinger Health System in Danville, Penn., and her colleagues followed 1,287 nondiabetic incident rheumatoid arthritis patients identified during January 2001–March 2008 at a rural tertiary health center.

The researchers compared the 884 patients who had never used TNF inhibitors with the 403 patients who had ever used them. Patients in the ever-use group had a higher median body mass index and C-reactive protein (CRP) level than did the never-use group, but these differences were not significant.

After a median follow-up time of 35 months for the ever users and 23 months for the never users, the researchers identified 13 new cases of diabetes in the ever-use group and 43 in the never-use group, for incidence rates of 11/1,000 and 22/1,000 person-years, respectively.

The median age of the patients was 61 years, the median BMI was 28.6 kg/m

Dr. Antohe had no financial conflicts to disclose. Several of her co-investigators have received research grants from pharmaceutical companies including Wyeth, Amgen, and Centocor.

ATLANTA — Use of tumor necrosis factor inhibitors reduced the risk of developing type 2 diabetes by 60% in a single-center study.

Dr. Jana Antohe of Geisinger Health System in Danville, Penn., and her colleagues followed 1,287 nondiabetic incident rheumatoid arthritis patients identified during January 2001–March 2008 at a rural tertiary health center.

The researchers compared the 884 patients who had never used TNF inhibitors with the 403 patients who had ever used them. Patients in the ever-use group had a higher median body mass index and C-reactive protein (CRP) level than did the never-use group, but these differences were not significant.

After a median follow-up time of 35 months for the ever users and 23 months for the never users, the researchers identified 13 new cases of diabetes in the ever-use group and 43 in the never-use group, for incidence rates of 11/1,000 and 22/1,000 person-years, respectively.

The median age of the patients was 61 years, the median BMI was 28.6 kg/m

Dr. Antohe had no financial conflicts to disclose. Several of her co-investigators have received research grants from pharmaceutical companies including Wyeth, Amgen, and Centocor.

NEW ORLEANS – Pregnant women who used proton pump inhibitors for gastroesophageal reflux during the first trimester of pregnancy were more than twice as likely to have babies with cardiac defects than were pregnant women who did not use PPIs, based on a retrospective study of 200,000 women.

Previous data have indicated a nonsignificant trend toward an association between use of proton pump inhibitors (PPIs) early in pregnancy and cardiac malformations, Dr. Andrew D. Rhim of the University of Pennsylvania in Philadelphia said in his presentation.

“Before this study, there were very limited human data [on risk], and this study suggests a possible increased risk of cardiovascular defects,” Dr. Jennifer Niebyl of the University of Iowa, Iowa City, said in an interview. A prospective study is needed to confirm these results, which are hampered by uncertainties surrounding the trimester of exposure and possible selection bias.

Dr. Niebyl and her colleagues conducted a study of 3,458 women that suggested metoclopramide may be a safe option for pregnant women (N. Engl. J. Med. 2009;360:2528-35). She advised that pregnant women avoid PPIs during the first trimester.

From a database of 208,951 pregnancies, Dr. Rhim and his colleagues identified 2,445 cases of cardiac malformations in newborns and compared them with 19,530 matched controls. All the newborns were registered between 2000 and 2008 in The Health Improvement Network, a database of information collected by general practitioners in the United Kingdom. “We found 130 instances of a PPI being prescribed within the first trimester” in the women who gave birth to infants with cardiac birth defects, Dr. Rhim said. After adjustment for multiple variables including maternal BMI, smoking status, alcohol use, and use of other medications, the risk for cardiac birth defects remained significant (odds ratio, 2.14). A history of cardiac malformations or diabetes in the mother was associated with a significantly increased risk of a cardiac defect in the baby.

The researchers identified septal, left ventricular, and right ventricular defects.

Dr. Rhim said that he had no financial conflicts to disclose.

View on the News

Timing Is Very Important

Retrospective case-control studies can show associations, but they cannot determine if the associations are causal. Moreover, such studies have major limitations, including selection bias, recall bias and timing of exposures, Timing is very important. For example, closure of the ventricular septum occurs by 6 weeks post conception, so an exposure that causes a ventricular septal defect (VSD) must occur before 6 weeks.

Consider the animal reproduction data included by manufacturers in package inserts. None of the six PPIs in the United States (dexlansoprazole [Dexilant], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec], pantoprazole [Protonix], and rabeprazole [Aciphex]) cause structural defects in animals. This is important: With only two exceptions, all known human teratogens also are teratogenic in animals.

I know of no studies that have shown a significant association between PPIs and cardiac defects. Atrial septal defects and VSDs are among the most common cardiac defects. VSDs are among the most common birth defects.

GERALD BRIGGS is clinical professor of pharmacy at the University of California, San Francisco.

NEW ORLEANS – Pregnant women who used proton pump inhibitors for gastroesophageal reflux during the first trimester of pregnancy were more than twice as likely to have babies with cardiac defects than were pregnant women who did not use PPIs, based on a retrospective study of 200,000 women.

Previous data have indicated a nonsignificant trend toward an association between use of proton pump inhibitors (PPIs) early in pregnancy and cardiac malformations, Dr. Andrew D. Rhim of the University of Pennsylvania in Philadelphia said in his presentation.

“Before this study, there were very limited human data [on risk], and this study suggests a possible increased risk of cardiovascular defects,” Dr. Jennifer Niebyl of the University of Iowa, Iowa City, said in an interview. A prospective study is needed to confirm these results, which are hampered by uncertainties surrounding the trimester of exposure and possible selection bias.

Dr. Niebyl and her colleagues conducted a study of 3,458 women that suggested metoclopramide may be a safe option for pregnant women (N. Engl. J. Med. 2009;360:2528-35). She advised that pregnant women avoid PPIs during the first trimester.

From a database of 208,951 pregnancies, Dr. Rhim and his colleagues identified 2,445 cases of cardiac malformations in newborns and compared them with 19,530 matched controls. All the newborns were registered between 2000 and 2008 in The Health Improvement Network, a database of information collected by general practitioners in the United Kingdom. “We found 130 instances of a PPI being prescribed within the first trimester” in the women who gave birth to infants with cardiac birth defects, Dr. Rhim said. After adjustment for multiple variables including maternal BMI, smoking status, alcohol use, and use of other medications, the risk for cardiac birth defects remained significant (odds ratio, 2.14). A history of cardiac malformations or diabetes in the mother was associated with a significantly increased risk of a cardiac defect in the baby.

The researchers identified septal, left ventricular, and right ventricular defects.

Dr. Rhim said that he had no financial conflicts to disclose.

View on the News

Timing Is Very Important

Retrospective case-control studies can show associations, but they cannot determine if the associations are causal. Moreover, such studies have major limitations, including selection bias, recall bias and timing of exposures, Timing is very important. For example, closure of the ventricular septum occurs by 6 weeks post conception, so an exposure that causes a ventricular septal defect (VSD) must occur before 6 weeks.

Consider the animal reproduction data included by manufacturers in package inserts. None of the six PPIs in the United States (dexlansoprazole [Dexilant], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec], pantoprazole [Protonix], and rabeprazole [Aciphex]) cause structural defects in animals. This is important: With only two exceptions, all known human teratogens also are teratogenic in animals.

I know of no studies that have shown a significant association between PPIs and cardiac defects. Atrial septal defects and VSDs are among the most common cardiac defects. VSDs are among the most common birth defects.

GERALD BRIGGS is clinical professor of pharmacy at the University of California, San Francisco.

NEW ORLEANS – Pregnant women who used proton pump inhibitors for gastroesophageal reflux during the first trimester of pregnancy were more than twice as likely to have babies with cardiac defects than were pregnant women who did not use PPIs, based on a retrospective study of 200,000 women.

Previous data have indicated a nonsignificant trend toward an association between use of proton pump inhibitors (PPIs) early in pregnancy and cardiac malformations, Dr. Andrew D. Rhim of the University of Pennsylvania in Philadelphia said in his presentation.

“Before this study, there were very limited human data [on risk], and this study suggests a possible increased risk of cardiovascular defects,” Dr. Jennifer Niebyl of the University of Iowa, Iowa City, said in an interview. A prospective study is needed to confirm these results, which are hampered by uncertainties surrounding the trimester of exposure and possible selection bias.

Dr. Niebyl and her colleagues conducted a study of 3,458 women that suggested metoclopramide may be a safe option for pregnant women (N. Engl. J. Med. 2009;360:2528-35). She advised that pregnant women avoid PPIs during the first trimester.

From a database of 208,951 pregnancies, Dr. Rhim and his colleagues identified 2,445 cases of cardiac malformations in newborns and compared them with 19,530 matched controls. All the newborns were registered between 2000 and 2008 in The Health Improvement Network, a database of information collected by general practitioners in the United Kingdom. “We found 130 instances of a PPI being prescribed within the first trimester” in the women who gave birth to infants with cardiac birth defects, Dr. Rhim said. After adjustment for multiple variables including maternal BMI, smoking status, alcohol use, and use of other medications, the risk for cardiac birth defects remained significant (odds ratio, 2.14). A history of cardiac malformations or diabetes in the mother was associated with a significantly increased risk of a cardiac defect in the baby.

The researchers identified septal, left ventricular, and right ventricular defects.

Dr. Rhim said that he had no financial conflicts to disclose.

View on the News

Timing Is Very Important

Retrospective case-control studies can show associations, but they cannot determine if the associations are causal. Moreover, such studies have major limitations, including selection bias, recall bias and timing of exposures, Timing is very important. For example, closure of the ventricular septum occurs by 6 weeks post conception, so an exposure that causes a ventricular septal defect (VSD) must occur before 6 weeks.

Consider the animal reproduction data included by manufacturers in package inserts. None of the six PPIs in the United States (dexlansoprazole [Dexilant], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec], pantoprazole [Protonix], and rabeprazole [Aciphex]) cause structural defects in animals. This is important: With only two exceptions, all known human teratogens also are teratogenic in animals.

I know of no studies that have shown a significant association between PPIs and cardiac defects. Atrial septal defects and VSDs are among the most common cardiac defects. VSDs are among the most common birth defects.

GERALD BRIGGS is clinical professor of pharmacy at the University of California, San Francisco.

ATLANTA — Lupus patients were more than 2.5 times as likely as the general population to develop blood cancers, based on data from 13,492 adults with lupus.

The risk for hematologic cancers was significantly elevated among patients with lupus. Specifically, lupus patients were more than three times as likely as the general population to develop any type of lymphoma, and more than three times as likely to develop non-Hodgkin's lymphoma. In addition, lupus patients were 1.15 times more likely than the general population to develop any cancer, said Dr. Sasha R. Bernatsky of the divisions of clinical epidemiology and rheumatology at McGill University in Montreal.

Previous studies have shown an association between systemic lupus erythematosus (SLE) and cancer, due largely to the increased risk for lymphoma. In this study, Dr. Bernatsky and her colleagues aimed for a more precise estimate of cancer rates in lupus patients, as well as stratification by age. This global effort included researchers from the Systemic Lupus International Collaborating Clinics, the Canadian Network for Improved Outcomes in SLE, and other sites around the world.

Dr. Bernatsky and her colleagues reviewed data on patients from 24 centers worldwide for an average follow-up period of 9 years, and a total of 118,359 patient-years. They identified 632 cancers during the study period.

The researchers also found a significantly increased risk of lung cancer, vulvovaginal cancer, and hepatic cancer in lupus patients, compared with the general population.

However, there was a significant decrease in the risk of hormone-sensitive cancers, including breast cancer, endometrial cancer, and ovarian cancer.

Altered clearance of viruses such as human papillomavirus might be behind the increased risk for cervical and vulvovaginal cancers in lupus patients, suggested Dr. Bernatsky. Changes in estrogen metabolism might be behind the decreased risk for hormone-sensitive cancers, although more research is needed to study these possible associations.

When the results were stratified by age, patients in the youngest age group (younger than 40 years) were significantly (1.7 times) more likely to develop any cancer compared with the general population.

Despite the increase in risk, blood cancers remain rare in lupus patients, Dr. Bernatsky noted. But the study results highlight the overall risk of cancer in lupus patients. The findings remind clinicians to counsel smoking cessation to reduce the risk of lung cancer.

The decreased risk of certain cancers such as breast cancer is good news for women with SLE “and will be an area of keen research interest in the future,” Dr. Bernatsky said.

She disclosed that she has received funding from the National Institutes of Health and research grants from the Arthritis Society of Canada.

Lupus patients have significantly higher risks for blood, lung, vulvovaginal, and hepatic cancer, said Dr. Sasha R. Bernatsky.

Source Heidi Splete/Elsevier Global Medical News

ATLANTA — Lupus patients were more than 2.5 times as likely as the general population to develop blood cancers, based on data from 13,492 adults with lupus.

The risk for hematologic cancers was significantly elevated among patients with lupus. Specifically, lupus patients were more than three times as likely as the general population to develop any type of lymphoma, and more than three times as likely to develop non-Hodgkin's lymphoma. In addition, lupus patients were 1.15 times more likely than the general population to develop any cancer, said Dr. Sasha R. Bernatsky of the divisions of clinical epidemiology and rheumatology at McGill University in Montreal.

Previous studies have shown an association between systemic lupus erythematosus (SLE) and cancer, due largely to the increased risk for lymphoma. In this study, Dr. Bernatsky and her colleagues aimed for a more precise estimate of cancer rates in lupus patients, as well as stratification by age. This global effort included researchers from the Systemic Lupus International Collaborating Clinics, the Canadian Network for Improved Outcomes in SLE, and other sites around the world.

Dr. Bernatsky and her colleagues reviewed data on patients from 24 centers worldwide for an average follow-up period of 9 years, and a total of 118,359 patient-years. They identified 632 cancers during the study period.

The researchers also found a significantly increased risk of lung cancer, vulvovaginal cancer, and hepatic cancer in lupus patients, compared with the general population.

However, there was a significant decrease in the risk of hormone-sensitive cancers, including breast cancer, endometrial cancer, and ovarian cancer.

Altered clearance of viruses such as human papillomavirus might be behind the increased risk for cervical and vulvovaginal cancers in lupus patients, suggested Dr. Bernatsky. Changes in estrogen metabolism might be behind the decreased risk for hormone-sensitive cancers, although more research is needed to study these possible associations.

When the results were stratified by age, patients in the youngest age group (younger than 40 years) were significantly (1.7 times) more likely to develop any cancer compared with the general population.

Despite the increase in risk, blood cancers remain rare in lupus patients, Dr. Bernatsky noted. But the study results highlight the overall risk of cancer in lupus patients. The findings remind clinicians to counsel smoking cessation to reduce the risk of lung cancer.

The decreased risk of certain cancers such as breast cancer is good news for women with SLE “and will be an area of keen research interest in the future,” Dr. Bernatsky said.

She disclosed that she has received funding from the National Institutes of Health and research grants from the Arthritis Society of Canada.

Lupus patients have significantly higher risks for blood, lung, vulvovaginal, and hepatic cancer, said Dr. Sasha R. Bernatsky.

Source Heidi Splete/Elsevier Global Medical News

ATLANTA — Lupus patients were more than 2.5 times as likely as the general population to develop blood cancers, based on data from 13,492 adults with lupus.

The risk for hematologic cancers was significantly elevated among patients with lupus. Specifically, lupus patients were more than three times as likely as the general population to develop any type of lymphoma, and more than three times as likely to develop non-Hodgkin's lymphoma. In addition, lupus patients were 1.15 times more likely than the general population to develop any cancer, said Dr. Sasha R. Bernatsky of the divisions of clinical epidemiology and rheumatology at McGill University in Montreal.

Previous studies have shown an association between systemic lupus erythematosus (SLE) and cancer, due largely to the increased risk for lymphoma. In this study, Dr. Bernatsky and her colleagues aimed for a more precise estimate of cancer rates in lupus patients, as well as stratification by age. This global effort included researchers from the Systemic Lupus International Collaborating Clinics, the Canadian Network for Improved Outcomes in SLE, and other sites around the world.

Dr. Bernatsky and her colleagues reviewed data on patients from 24 centers worldwide for an average follow-up period of 9 years, and a total of 118,359 patient-years. They identified 632 cancers during the study period.

The researchers also found a significantly increased risk of lung cancer, vulvovaginal cancer, and hepatic cancer in lupus patients, compared with the general population.

However, there was a significant decrease in the risk of hormone-sensitive cancers, including breast cancer, endometrial cancer, and ovarian cancer.

Altered clearance of viruses such as human papillomavirus might be behind the increased risk for cervical and vulvovaginal cancers in lupus patients, suggested Dr. Bernatsky. Changes in estrogen metabolism might be behind the decreased risk for hormone-sensitive cancers, although more research is needed to study these possible associations.

When the results were stratified by age, patients in the youngest age group (younger than 40 years) were significantly (1.7 times) more likely to develop any cancer compared with the general population.

Despite the increase in risk, blood cancers remain rare in lupus patients, Dr. Bernatsky noted. But the study results highlight the overall risk of cancer in lupus patients. The findings remind clinicians to counsel smoking cessation to reduce the risk of lung cancer.

The decreased risk of certain cancers such as breast cancer is good news for women with SLE “and will be an area of keen research interest in the future,” Dr. Bernatsky said.

She disclosed that she has received funding from the National Institutes of Health and research grants from the Arthritis Society of Canada.

Lupus patients have significantly higher risks for blood, lung, vulvovaginal, and hepatic cancer, said Dr. Sasha R. Bernatsky.

Source Heidi Splete/Elsevier Global Medical News

ATLANTA — Atorvastatin did not prevent early atherosclerosis in children and adolescents with lupus, based on data from 221 patients aged 10–21 years.

“This is a landmark study in the pediatric rheumatology community,” said Dr. Laura Schanberg, co-chief of the division of pediatric rheumatology at Duke University Medical Center in Durham, N.C.

To assess the risk of cardiovascular problems, the researchers used an accepted surrogate marker: an ultrasound measurement of the thickening of the carotid arteries. The study participants underwent ultrasound examinations seven times during the 3-year study period.

Overall, progression of thickening in the arteries was not significantly different between the statin and placebo groups.

“This was a surprise to us,” Dr. Schanberg said. The researchers had expected significantly less carotid intima-media thickening (CIMT) in the statin group.

The data were trending toward a positive effect, but the findings did not show enough benefit to recommend routine statin treatment for most children and adolescents with lupus. The difference in CIMT was 0.0010 mm/year in the statin group, vs. 0.0024 mm/year in the placebo group (P =.24).

The statin group did achieve statistically significant reductions in high-sensitivity C-reactive protein levels, total cholesterol, and low-density lipoprotein. Changes in lupus disease activity and damage, quality of life measures, and measures of muscle, liver, and neurotoxicity were similar between the two groups.

Previous studies have shown that lupus is a strong risk factor for cardiovascular problems. Pediatric lupus patients are considered at increased risk because they typically live with the disease for a longer period of time. Statins have not previously been studied as a way to reduce cardiovascular risk in children with lupus, but some clinicians already prescribe statins to children with lupus at especially high risk from factors such as high cholesterol, Dr. Schanberg said.

“We wanted to see whether there was a way to decrease the long-term risk” of cardiovascular problems in children with lupus, she said. In this study, the researchers enrolled patients from 21 sites through the Childhood Arthritis and Rheumatology Research Alliance.

All the children received standard lupus care including aspirin, a multivitamin, hydroxychloroquine, and counseling about a low-cholesterol diet and other cardiovascular risk factors. They were randomized to receive atorvastatin or a placebo.

Of note, the study did not include children at especially high risk for cardiovascular problems, such as those with high cholesterol, she said. In fact, a subgroup analysis may reveal certain groups that would benefit from statin use in childhood and adolescence, she said.

Despite the lack of clinical significance, the results showed that atorvastatin was safe and well tolerated in the study population, and Dr. Schanberg advised clinicians to continue prescribing statins for pediatric lupus patients with abnormal cholesterol or lipid levels.

Dr. Schanberg has served on the advisory board for Bristol-Myers Squibb, and Pfizer provided the drugs used in the study.

Less carotid intima-media thickening was expected in the statin group, notes Dr. Laura Schanberg at

Source Heidi Splete/Elsevier Global Medical Newswww.rheumatologynews.com

ATLANTA — Atorvastatin did not prevent early atherosclerosis in children and adolescents with lupus, based on data from 221 patients aged 10–21 years.

“This is a landmark study in the pediatric rheumatology community,” said Dr. Laura Schanberg, co-chief of the division of pediatric rheumatology at Duke University Medical Center in Durham, N.C.

To assess the risk of cardiovascular problems, the researchers used an accepted surrogate marker: an ultrasound measurement of the thickening of the carotid arteries. The study participants underwent ultrasound examinations seven times during the 3-year study period.

Overall, progression of thickening in the arteries was not significantly different between the statin and placebo groups.

“This was a surprise to us,” Dr. Schanberg said. The researchers had expected significantly less carotid intima-media thickening (CIMT) in the statin group.

The data were trending toward a positive effect, but the findings did not show enough benefit to recommend routine statin treatment for most children and adolescents with lupus. The difference in CIMT was 0.0010 mm/year in the statin group, vs. 0.0024 mm/year in the placebo group (P =.24).

The statin group did achieve statistically significant reductions in high-sensitivity C-reactive protein levels, total cholesterol, and low-density lipoprotein. Changes in lupus disease activity and damage, quality of life measures, and measures of muscle, liver, and neurotoxicity were similar between the two groups.

Previous studies have shown that lupus is a strong risk factor for cardiovascular problems. Pediatric lupus patients are considered at increased risk because they typically live with the disease for a longer period of time. Statins have not previously been studied as a way to reduce cardiovascular risk in children with lupus, but some clinicians already prescribe statins to children with lupus at especially high risk from factors such as high cholesterol, Dr. Schanberg said.

“We wanted to see whether there was a way to decrease the long-term risk” of cardiovascular problems in children with lupus, she said. In this study, the researchers enrolled patients from 21 sites through the Childhood Arthritis and Rheumatology Research Alliance.

All the children received standard lupus care including aspirin, a multivitamin, hydroxychloroquine, and counseling about a low-cholesterol diet and other cardiovascular risk factors. They were randomized to receive atorvastatin or a placebo.

Of note, the study did not include children at especially high risk for cardiovascular problems, such as those with high cholesterol, she said. In fact, a subgroup analysis may reveal certain groups that would benefit from statin use in childhood and adolescence, she said.

Despite the lack of clinical significance, the results showed that atorvastatin was safe and well tolerated in the study population, and Dr. Schanberg advised clinicians to continue prescribing statins for pediatric lupus patients with abnormal cholesterol or lipid levels.

Dr. Schanberg has served on the advisory board for Bristol-Myers Squibb, and Pfizer provided the drugs used in the study.

Less carotid intima-media thickening was expected in the statin group, notes Dr. Laura Schanberg at

Source Heidi Splete/Elsevier Global Medical Newswww.rheumatologynews.com

ATLANTA — Atorvastatin did not prevent early atherosclerosis in children and adolescents with lupus, based on data from 221 patients aged 10–21 years.

“This is a landmark study in the pediatric rheumatology community,” said Dr. Laura Schanberg, co-chief of the division of pediatric rheumatology at Duke University Medical Center in Durham, N.C.

To assess the risk of cardiovascular problems, the researchers used an accepted surrogate marker: an ultrasound measurement of the thickening of the carotid arteries. The study participants underwent ultrasound examinations seven times during the 3-year study period.

Overall, progression of thickening in the arteries was not significantly different between the statin and placebo groups.

“This was a surprise to us,” Dr. Schanberg said. The researchers had expected significantly less carotid intima-media thickening (CIMT) in the statin group.

The data were trending toward a positive effect, but the findings did not show enough benefit to recommend routine statin treatment for most children and adolescents with lupus. The difference in CIMT was 0.0010 mm/year in the statin group, vs. 0.0024 mm/year in the placebo group (P =.24).

The statin group did achieve statistically significant reductions in high-sensitivity C-reactive protein levels, total cholesterol, and low-density lipoprotein. Changes in lupus disease activity and damage, quality of life measures, and measures of muscle, liver, and neurotoxicity were similar between the two groups.

Previous studies have shown that lupus is a strong risk factor for cardiovascular problems. Pediatric lupus patients are considered at increased risk because they typically live with the disease for a longer period of time. Statins have not previously been studied as a way to reduce cardiovascular risk in children with lupus, but some clinicians already prescribe statins to children with lupus at especially high risk from factors such as high cholesterol, Dr. Schanberg said.

“We wanted to see whether there was a way to decrease the long-term risk” of cardiovascular problems in children with lupus, she said. In this study, the researchers enrolled patients from 21 sites through the Childhood Arthritis and Rheumatology Research Alliance.

All the children received standard lupus care including aspirin, a multivitamin, hydroxychloroquine, and counseling about a low-cholesterol diet and other cardiovascular risk factors. They were randomized to receive atorvastatin or a placebo.

Of note, the study did not include children at especially high risk for cardiovascular problems, such as those with high cholesterol, she said. In fact, a subgroup analysis may reveal certain groups that would benefit from statin use in childhood and adolescence, she said.

Despite the lack of clinical significance, the results showed that atorvastatin was safe and well tolerated in the study population, and Dr. Schanberg advised clinicians to continue prescribing statins for pediatric lupus patients with abnormal cholesterol or lipid levels.

Dr. Schanberg has served on the advisory board for Bristol-Myers Squibb, and Pfizer provided the drugs used in the study.

Less carotid intima-media thickening was expected in the statin group, notes Dr. Laura Schanberg at

Source Heidi Splete/Elsevier Global Medical Newswww.rheumatologynews.com