Nancy Walsh

MINNEAPOLIS — Data from a surveillance system in Maryland show the burden of unintended pregnancy remains large, with multiple potential risks for mothers and infants, according to Dr. Diana Cheng of the Maryland Department of Health and Mental Hygiene, Baltimore.

The Maryland Pregnancy Risk Assessment Monitoring System (PRAMS) was established by the Centers for Disease Control and Prevention to obtain information about maternal behaviors and experiences that may be associated with adverse pregnancy outcomes.

Between 2001 and 2005, a random sample of 7,381 mothers did the PRAMS survey 2–6 months after delivery. The survey included the following question: Thinking back to just before you got pregnant, how did you feel about becoming pregnant? Available answers were “I wanted to be pregnant sooner,” “I wanted to be pregnant later,” “I wanted to be pregnant then,” or “I didn't want to be pregnant then or at any time in the future.”

Pregnancies were classified as intended if the mothers had wanted them then or sooner and as unintended if they said they wanted them later or not at all.

Analysis of the responses showed that 58% of the pregnancies were intended and 42% were unintended, Dr. Cheng said at the annual meeting of the Association of Reproductive Health Professionals.

In women with intended pregnancies, 16% said they wanted their pregnancy sooner and 42% said they wanted their pregnancy then. In those with unintended pregnancies, 31% said they wanted their pregnancies later and 11% said they didn't want to be pregnant then or ever.

Of those whose pregnancies were unwanted, 86% did not take folic acid daily, 44% initiated prenatal care after the first trimester, and 24% smoked during pregnancy. Post partum, 37% did not breast-feed, 30% smoked, 27% reported depression, and 50% did not place their babies on their backs to sleep. Moreover, 11% of women in this group reported a history of physical abuse.

In women with intended pregnancies, by contrast, significantly lower percentages engaged in unhealthy behaviors. For example, in this group, 87% initiated prenatal care during the first trimester, 81% breast-fed, and 69% placed their babies on their backs for sleep.

A total of 10% of babies born to mothers whose pregnancies were unwanted were of low birth weight, as were 7% of babies born to mothers whose pregnancies were intended.

The survey also found that 43% of the women were using birth control at the time they became pregnant. Among the women who did not use birth control, most said they did not think they could get pregnant at that time. Improving women's access to education about contraception will help couples better plan pregnancies and increase the rates of intended pregnancies, she said.

MINNEAPOLIS — Data from a surveillance system in Maryland show the burden of unintended pregnancy remains large, with multiple potential risks for mothers and infants, according to Dr. Diana Cheng of the Maryland Department of Health and Mental Hygiene, Baltimore.

The Maryland Pregnancy Risk Assessment Monitoring System (PRAMS) was established by the Centers for Disease Control and Prevention to obtain information about maternal behaviors and experiences that may be associated with adverse pregnancy outcomes.

Between 2001 and 2005, a random sample of 7,381 mothers did the PRAMS survey 2–6 months after delivery. The survey included the following question: Thinking back to just before you got pregnant, how did you feel about becoming pregnant? Available answers were “I wanted to be pregnant sooner,” “I wanted to be pregnant later,” “I wanted to be pregnant then,” or “I didn't want to be pregnant then or at any time in the future.”

Pregnancies were classified as intended if the mothers had wanted them then or sooner and as unintended if they said they wanted them later or not at all.

Analysis of the responses showed that 58% of the pregnancies were intended and 42% were unintended, Dr. Cheng said at the annual meeting of the Association of Reproductive Health Professionals.

In women with intended pregnancies, 16% said they wanted their pregnancy sooner and 42% said they wanted their pregnancy then. In those with unintended pregnancies, 31% said they wanted their pregnancies later and 11% said they didn't want to be pregnant then or ever.

Of those whose pregnancies were unwanted, 86% did not take folic acid daily, 44% initiated prenatal care after the first trimester, and 24% smoked during pregnancy. Post partum, 37% did not breast-feed, 30% smoked, 27% reported depression, and 50% did not place their babies on their backs to sleep. Moreover, 11% of women in this group reported a history of physical abuse.

In women with intended pregnancies, by contrast, significantly lower percentages engaged in unhealthy behaviors. For example, in this group, 87% initiated prenatal care during the first trimester, 81% breast-fed, and 69% placed their babies on their backs for sleep.

A total of 10% of babies born to mothers whose pregnancies were unwanted were of low birth weight, as were 7% of babies born to mothers whose pregnancies were intended.

The survey also found that 43% of the women were using birth control at the time they became pregnant. Among the women who did not use birth control, most said they did not think they could get pregnant at that time. Improving women's access to education about contraception will help couples better plan pregnancies and increase the rates of intended pregnancies, she said.

MINNEAPOLIS — Data from a surveillance system in Maryland show the burden of unintended pregnancy remains large, with multiple potential risks for mothers and infants, according to Dr. Diana Cheng of the Maryland Department of Health and Mental Hygiene, Baltimore.

The Maryland Pregnancy Risk Assessment Monitoring System (PRAMS) was established by the Centers for Disease Control and Prevention to obtain information about maternal behaviors and experiences that may be associated with adverse pregnancy outcomes.

Between 2001 and 2005, a random sample of 7,381 mothers did the PRAMS survey 2–6 months after delivery. The survey included the following question: Thinking back to just before you got pregnant, how did you feel about becoming pregnant? Available answers were “I wanted to be pregnant sooner,” “I wanted to be pregnant later,” “I wanted to be pregnant then,” or “I didn't want to be pregnant then or at any time in the future.”

Pregnancies were classified as intended if the mothers had wanted them then or sooner and as unintended if they said they wanted them later or not at all.

Analysis of the responses showed that 58% of the pregnancies were intended and 42% were unintended, Dr. Cheng said at the annual meeting of the Association of Reproductive Health Professionals.

In women with intended pregnancies, 16% said they wanted their pregnancy sooner and 42% said they wanted their pregnancy then. In those with unintended pregnancies, 31% said they wanted their pregnancies later and 11% said they didn't want to be pregnant then or ever.

Of those whose pregnancies were unwanted, 86% did not take folic acid daily, 44% initiated prenatal care after the first trimester, and 24% smoked during pregnancy. Post partum, 37% did not breast-feed, 30% smoked, 27% reported depression, and 50% did not place their babies on their backs to sleep. Moreover, 11% of women in this group reported a history of physical abuse.

In women with intended pregnancies, by contrast, significantly lower percentages engaged in unhealthy behaviors. For example, in this group, 87% initiated prenatal care during the first trimester, 81% breast-fed, and 69% placed their babies on their backs for sleep.

A total of 10% of babies born to mothers whose pregnancies were unwanted were of low birth weight, as were 7% of babies born to mothers whose pregnancies were intended.

The survey also found that 43% of the women were using birth control at the time they became pregnant. Among the women who did not use birth control, most said they did not think they could get pregnant at that time. Improving women's access to education about contraception will help couples better plan pregnancies and increase the rates of intended pregnancies, she said.

BOSTON — The adolescent HIV-1 epidemic as reflected in a multisite cohort of U.S. youth is changing from one of vertically transmitted infection to one where infection is acquired through risk behaviors, posing new challenges for providers and the health care system, said Dr. Allison L. Agwu in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

The HIV Research Network, a consortium of 21 clinical sites providing primary HIV care, includes 684 patients aged 12–24 years. Vertical transmission was the source of infection in 227 patients and risk behaviors accounted for 457 cases, said Dr. Agwu of Johns Hopkins University, Baltimore.

Analysis of data from this cohort showed patients infected through risk behaviors are older, with a median age of 22 years, compared with a median age of 15 years in vertical-transmission patients. They are also more likely to be male. Of the risk-behavior patients, 292 (64%) are male, as are 108 (48%) of the vertical-transmission patients.

Risk behaviors comprised men having sex with men (51%), unprotected heterosexual activity (45%), and IV drug use (4%).

The median CD4 count in the risk-behavior group was 492 cells/mm

Despite this worse immune suppression and higher levels of viremia in the risk-behavior patients, they were less likely to be on highly active antiretroviral therapy (HAART) (43% vs. 88%). Those infected through risk behaviors also had significantly fewer outpatient visits, averaging five visits a year, whereas vertical-transmission patients averaged seven visits.

Rates of hospitalization did not differ, at 19/100 patient-years in the risk-behavior group and 17/100 patient-years in the vertical-transmission group, Dr. Agwu reported at the meeting, sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention. Other aspects of treatment also did not differ significantly between the two groups. For example, 89% of those meeting the criteria for prophylaxis against Pneumocystis carinii pneumonia in the risk-behavior group received prophylaxis, as did 80% of vertical-transmission patients.

Differences in psychosocial risk factors between the two groups might account for the varying rates of HAART use, Dr. Agwu said in an interview. “[We'll] focus on deciphering patient and provider barriers to HAART initiation in the risk-behavior group to institute appropriate interventions.” She added that the number of risk behavior patients in need of treatment is likely to grow as the Centers for Disease Control and Prevention's recommendation of universal opt-out testing is implemented.

BOSTON — The adolescent HIV-1 epidemic as reflected in a multisite cohort of U.S. youth is changing from one of vertically transmitted infection to one where infection is acquired through risk behaviors, posing new challenges for providers and the health care system, said Dr. Allison L. Agwu in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

The HIV Research Network, a consortium of 21 clinical sites providing primary HIV care, includes 684 patients aged 12–24 years. Vertical transmission was the source of infection in 227 patients and risk behaviors accounted for 457 cases, said Dr. Agwu of Johns Hopkins University, Baltimore.

Analysis of data from this cohort showed patients infected through risk behaviors are older, with a median age of 22 years, compared with a median age of 15 years in vertical-transmission patients. They are also more likely to be male. Of the risk-behavior patients, 292 (64%) are male, as are 108 (48%) of the vertical-transmission patients.

Risk behaviors comprised men having sex with men (51%), unprotected heterosexual activity (45%), and IV drug use (4%).

The median CD4 count in the risk-behavior group was 492 cells/mm

Despite this worse immune suppression and higher levels of viremia in the risk-behavior patients, they were less likely to be on highly active antiretroviral therapy (HAART) (43% vs. 88%). Those infected through risk behaviors also had significantly fewer outpatient visits, averaging five visits a year, whereas vertical-transmission patients averaged seven visits.

Rates of hospitalization did not differ, at 19/100 patient-years in the risk-behavior group and 17/100 patient-years in the vertical-transmission group, Dr. Agwu reported at the meeting, sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention. Other aspects of treatment also did not differ significantly between the two groups. For example, 89% of those meeting the criteria for prophylaxis against Pneumocystis carinii pneumonia in the risk-behavior group received prophylaxis, as did 80% of vertical-transmission patients.

Differences in psychosocial risk factors between the two groups might account for the varying rates of HAART use, Dr. Agwu said in an interview. “[We'll] focus on deciphering patient and provider barriers to HAART initiation in the risk-behavior group to institute appropriate interventions.” She added that the number of risk behavior patients in need of treatment is likely to grow as the Centers for Disease Control and Prevention's recommendation of universal opt-out testing is implemented.

BOSTON — The adolescent HIV-1 epidemic as reflected in a multisite cohort of U.S. youth is changing from one of vertically transmitted infection to one where infection is acquired through risk behaviors, posing new challenges for providers and the health care system, said Dr. Allison L. Agwu in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

The HIV Research Network, a consortium of 21 clinical sites providing primary HIV care, includes 684 patients aged 12–24 years. Vertical transmission was the source of infection in 227 patients and risk behaviors accounted for 457 cases, said Dr. Agwu of Johns Hopkins University, Baltimore.

Analysis of data from this cohort showed patients infected through risk behaviors are older, with a median age of 22 years, compared with a median age of 15 years in vertical-transmission patients. They are also more likely to be male. Of the risk-behavior patients, 292 (64%) are male, as are 108 (48%) of the vertical-transmission patients.

Risk behaviors comprised men having sex with men (51%), unprotected heterosexual activity (45%), and IV drug use (4%).

The median CD4 count in the risk-behavior group was 492 cells/mm

Despite this worse immune suppression and higher levels of viremia in the risk-behavior patients, they were less likely to be on highly active antiretroviral therapy (HAART) (43% vs. 88%). Those infected through risk behaviors also had significantly fewer outpatient visits, averaging five visits a year, whereas vertical-transmission patients averaged seven visits.

Rates of hospitalization did not differ, at 19/100 patient-years in the risk-behavior group and 17/100 patient-years in the vertical-transmission group, Dr. Agwu reported at the meeting, sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention. Other aspects of treatment also did not differ significantly between the two groups. For example, 89% of those meeting the criteria for prophylaxis against Pneumocystis carinii pneumonia in the risk-behavior group received prophylaxis, as did 80% of vertical-transmission patients.

Differences in psychosocial risk factors between the two groups might account for the varying rates of HAART use, Dr. Agwu said in an interview. “[We'll] focus on deciphering patient and provider barriers to HAART initiation in the risk-behavior group to institute appropriate interventions.” She added that the number of risk behavior patients in need of treatment is likely to grow as the Centers for Disease Control and Prevention's recommendation of universal opt-out testing is implemented.

TORONTO — Noninvasive mechanical ventilation alleviated respiratory distress in end-stage cancer patients in a randomized study that compared this palliative modality with the administration of oxygen, Dr. Stefano Nava reported at an international conference of the American Thoracic Society.

“In end-stage cancer we concentrate on relieving bodily pain with morphine, but we overlook the pain of the respiratory system, which is dyspnea,” said Dr. Nava, chief of the respiratory critical care unit at Instituto Scientifico di Pavia (Italy).

Oxygen is routinely administered along with morphine in this situation, but there has never been a randomized trial evaluating any technique for easing respiratory distress in these patients and there is no evidence that oxygen is actually beneficial, he said.

To address this uncertainty, the trial was undertaken in six European centers, comparing noninvasive mechanical ventilation (NIV) using a face mask to oxygen administered via nasal cannula. NIV involves the use of positive pressure to aid in breathing, as does conventional mechanical ventilation, but does not require intubation, Dr. Nava explained.

For enrollment in the study, patients had to have acute respiratory failure and distress, with a Borg dyspnea score greater than 3 and a respiratory rate exceeding 25 breaths per minute.

A total of 126 patients were randomized. All of them had solid cancers, and mortality was 80%, as expected, Dr. Nava said. Clearly, survival was not increased. “In fact, we explain to patients that NIV may unduly prolong life, even if only for a few hours,” he said.

Overall, there was a similar degree of relief in both groups, but the effects were more rapid with NIV. Borg dyspnea score in the NIV group fell significantly from 6.9 on admission to 5.7 at 1 hour, to 4.7 at 3 hours, and to 3.9 at 24 hours. By comparison, a significant decrease from 6.7 on admission to 5.5 was seen only at 3 hours and to 4.8 at 24 hours in the oxygen group.

Morphine use also was lower in the NIV group in the first 24 hours, at 12.2 mg/day, compared with 19.6 mg/day in the oxygen group. “This is important for patients, as it allows the sensorium to remain clearer and they are able to say goodbye and sign papers if necessary, which are not trivial things,” Dr. Nava commented in a press briefing.

With NIV, the mask is worn only intermittently, so the patient also can drink and eat if able. In Europe, NIV is now used for up to 40%–50% of ventilated patients in the intensive care unit, but it has not yet been widely adopted in North America, he said.

TORONTO — Noninvasive mechanical ventilation alleviated respiratory distress in end-stage cancer patients in a randomized study that compared this palliative modality with the administration of oxygen, Dr. Stefano Nava reported at an international conference of the American Thoracic Society.

“In end-stage cancer we concentrate on relieving bodily pain with morphine, but we overlook the pain of the respiratory system, which is dyspnea,” said Dr. Nava, chief of the respiratory critical care unit at Instituto Scientifico di Pavia (Italy).

Oxygen is routinely administered along with morphine in this situation, but there has never been a randomized trial evaluating any technique for easing respiratory distress in these patients and there is no evidence that oxygen is actually beneficial, he said.

To address this uncertainty, the trial was undertaken in six European centers, comparing noninvasive mechanical ventilation (NIV) using a face mask to oxygen administered via nasal cannula. NIV involves the use of positive pressure to aid in breathing, as does conventional mechanical ventilation, but does not require intubation, Dr. Nava explained.

For enrollment in the study, patients had to have acute respiratory failure and distress, with a Borg dyspnea score greater than 3 and a respiratory rate exceeding 25 breaths per minute.

A total of 126 patients were randomized. All of them had solid cancers, and mortality was 80%, as expected, Dr. Nava said. Clearly, survival was not increased. “In fact, we explain to patients that NIV may unduly prolong life, even if only for a few hours,” he said.

Overall, there was a similar degree of relief in both groups, but the effects were more rapid with NIV. Borg dyspnea score in the NIV group fell significantly from 6.9 on admission to 5.7 at 1 hour, to 4.7 at 3 hours, and to 3.9 at 24 hours. By comparison, a significant decrease from 6.7 on admission to 5.5 was seen only at 3 hours and to 4.8 at 24 hours in the oxygen group.

Morphine use also was lower in the NIV group in the first 24 hours, at 12.2 mg/day, compared with 19.6 mg/day in the oxygen group. “This is important for patients, as it allows the sensorium to remain clearer and they are able to say goodbye and sign papers if necessary, which are not trivial things,” Dr. Nava commented in a press briefing.

With NIV, the mask is worn only intermittently, so the patient also can drink and eat if able. In Europe, NIV is now used for up to 40%–50% of ventilated patients in the intensive care unit, but it has not yet been widely adopted in North America, he said.

TORONTO — Noninvasive mechanical ventilation alleviated respiratory distress in end-stage cancer patients in a randomized study that compared this palliative modality with the administration of oxygen, Dr. Stefano Nava reported at an international conference of the American Thoracic Society.

“In end-stage cancer we concentrate on relieving bodily pain with morphine, but we overlook the pain of the respiratory system, which is dyspnea,” said Dr. Nava, chief of the respiratory critical care unit at Instituto Scientifico di Pavia (Italy).

Oxygen is routinely administered along with morphine in this situation, but there has never been a randomized trial evaluating any technique for easing respiratory distress in these patients and there is no evidence that oxygen is actually beneficial, he said.

To address this uncertainty, the trial was undertaken in six European centers, comparing noninvasive mechanical ventilation (NIV) using a face mask to oxygen administered via nasal cannula. NIV involves the use of positive pressure to aid in breathing, as does conventional mechanical ventilation, but does not require intubation, Dr. Nava explained.

For enrollment in the study, patients had to have acute respiratory failure and distress, with a Borg dyspnea score greater than 3 and a respiratory rate exceeding 25 breaths per minute.

A total of 126 patients were randomized. All of them had solid cancers, and mortality was 80%, as expected, Dr. Nava said. Clearly, survival was not increased. “In fact, we explain to patients that NIV may unduly prolong life, even if only for a few hours,” he said.

Overall, there was a similar degree of relief in both groups, but the effects were more rapid with NIV. Borg dyspnea score in the NIV group fell significantly from 6.9 on admission to 5.7 at 1 hour, to 4.7 at 3 hours, and to 3.9 at 24 hours. By comparison, a significant decrease from 6.7 on admission to 5.5 was seen only at 3 hours and to 4.8 at 24 hours in the oxygen group.

Morphine use also was lower in the NIV group in the first 24 hours, at 12.2 mg/day, compared with 19.6 mg/day in the oxygen group. “This is important for patients, as it allows the sensorium to remain clearer and they are able to say goodbye and sign papers if necessary, which are not trivial things,” Dr. Nava commented in a press briefing.

With NIV, the mask is worn only intermittently, so the patient also can drink and eat if able. In Europe, NIV is now used for up to 40%–50% of ventilated patients in the intensive care unit, but it has not yet been widely adopted in North America, he said.

MINNEAPOLIS — A newer extended-regimen oral contraceptive that includes 7 days of low-dose estrogen rather than a week of placebo pills is associated with an improved bleeding pattern.

The newer formulation, known as Seasonique, was shown in a cross-study analysis of two phase III trials to be associated with fewer scheduled bleeding days and a reduction in breakthrough bleeding, compared with an older formulation called Seasonale, Dr. Andrew N. Kaunitz said at the annual meeting of the Association of Reproductive Health Professionals.

Both regimens include 84 days of 30 mcg ethinyl estradiol and 150 mcg of levonorgestrel, but Seasonique substitutes 7 days of 10 mcg ethinyl estradiol monotherapy for the 7 days of placebo in the Seasonale regimen. The two drugs are manufactured by Duramed Pharmaceuticals, and Dr. Kaunitz is a speaker or consultant for Duramed Pharmaceuticals and various others.

In the first of the two pivotal 1-year trials, 682 patients from 47 sites throughout the United States were randomized to receive Seasonale or the conventional 28-day oral contraceptive (OC) Nordette, which contains the same daily dose of hormones. The incidence of unscheduled bleeding initially was higher among patients on the extended-cycle regimen, but decreased throughout the study, said Dr. Kaunitz of the University of Florida, Jacksonville, who was one of the investigators in this trial.

By the end of the trial, the incidence of unscheduled bleeding in the extended-cycle regimen was comparable, at a median of 3.6% of days, to that in the conventional group, at 2.9% of days.

In the second study, Seasonique was evaluated in an open-label fashion among 1,006 women being treated at 36 U.S. sites. In this study, the median number of days of unscheduled bleeding in the first extended cycle was similar to that reported in the first trial, but decreased sharply in subsequent cycles. By cycle four, the median number of days of unscheduled bleeding was 0.3 on a per-patient-month basis.

Analysis of the data from these two studies showed that unscheduled bleeding and spotting decreased more quickly with the 91-day regimen that included low-dose estrogen, approaching significance in the second cycle and achieving significance in the third cycle, Dr. Kaunitz said.

Moreover, there were consistent differences in length of scheduled withdrawal bleeding episodes, with a median of 3 days for Seasonique and 4 days for Seasonale, he said.

“This was not a head-to-head study,” he cautioned. Nonetheless, the patient populations were comparable in baseline characteristics, race, age, prior OC use, smoking, and body mass index, and the pattern of unscheduled bleeding seen during the first 3-month cycle was identical across the two studies. Only after the first placebo or low-dose estrogen week was there a difference in bleeding pattern, so observations across the two studies should be valid, he said.

Previous research has found that there is a correlation between the amount of breakthrough bleeding and both higher endogenous 17-β estradiol levels and larger follicle size.

In a meta-analysis of seven prospective trials of various combination OC formulations, the pills that were associated with greater follicular suppression were also those that had improved bleeding profiles.

“Endrikat in Germany [lead author of this meta-analysis] speculated that a biologic mechanism explaining why better follicular suppression was associated with less intermenstrual bleeding might be that the endometrium of women on the pill is not only responsive to exogenous estrogen, as we traditionally thought, but also to the endogenous 17-β estradiol made by follicles during OC use,” he said.

In another study that compared follicular suppression by means of manipulation of the hormone-free interval with three different OC regimens, women receiving supplementation with 5 days of 10 mcg ethinyl estradiol had fewer and smaller follicles than women who had a 7-day hormone-free interval.

“I believe that my data add to Endrikat's hypothesis, that OCs that result in better follicular suppression can help women achieve better bleeding profiles,” Dr. Kaunitz said.

MINNEAPOLIS — A newer extended-regimen oral contraceptive that includes 7 days of low-dose estrogen rather than a week of placebo pills is associated with an improved bleeding pattern.

The newer formulation, known as Seasonique, was shown in a cross-study analysis of two phase III trials to be associated with fewer scheduled bleeding days and a reduction in breakthrough bleeding, compared with an older formulation called Seasonale, Dr. Andrew N. Kaunitz said at the annual meeting of the Association of Reproductive Health Professionals.

Both regimens include 84 days of 30 mcg ethinyl estradiol and 150 mcg of levonorgestrel, but Seasonique substitutes 7 days of 10 mcg ethinyl estradiol monotherapy for the 7 days of placebo in the Seasonale regimen. The two drugs are manufactured by Duramed Pharmaceuticals, and Dr. Kaunitz is a speaker or consultant for Duramed Pharmaceuticals and various others.

In the first of the two pivotal 1-year trials, 682 patients from 47 sites throughout the United States were randomized to receive Seasonale or the conventional 28-day oral contraceptive (OC) Nordette, which contains the same daily dose of hormones. The incidence of unscheduled bleeding initially was higher among patients on the extended-cycle regimen, but decreased throughout the study, said Dr. Kaunitz of the University of Florida, Jacksonville, who was one of the investigators in this trial.

By the end of the trial, the incidence of unscheduled bleeding in the extended-cycle regimen was comparable, at a median of 3.6% of days, to that in the conventional group, at 2.9% of days.

In the second study, Seasonique was evaluated in an open-label fashion among 1,006 women being treated at 36 U.S. sites. In this study, the median number of days of unscheduled bleeding in the first extended cycle was similar to that reported in the first trial, but decreased sharply in subsequent cycles. By cycle four, the median number of days of unscheduled bleeding was 0.3 on a per-patient-month basis.

Analysis of the data from these two studies showed that unscheduled bleeding and spotting decreased more quickly with the 91-day regimen that included low-dose estrogen, approaching significance in the second cycle and achieving significance in the third cycle, Dr. Kaunitz said.

Moreover, there were consistent differences in length of scheduled withdrawal bleeding episodes, with a median of 3 days for Seasonique and 4 days for Seasonale, he said.

“This was not a head-to-head study,” he cautioned. Nonetheless, the patient populations were comparable in baseline characteristics, race, age, prior OC use, smoking, and body mass index, and the pattern of unscheduled bleeding seen during the first 3-month cycle was identical across the two studies. Only after the first placebo or low-dose estrogen week was there a difference in bleeding pattern, so observations across the two studies should be valid, he said.

Previous research has found that there is a correlation between the amount of breakthrough bleeding and both higher endogenous 17-β estradiol levels and larger follicle size.

In a meta-analysis of seven prospective trials of various combination OC formulations, the pills that were associated with greater follicular suppression were also those that had improved bleeding profiles.

“Endrikat in Germany [lead author of this meta-analysis] speculated that a biologic mechanism explaining why better follicular suppression was associated with less intermenstrual bleeding might be that the endometrium of women on the pill is not only responsive to exogenous estrogen, as we traditionally thought, but also to the endogenous 17-β estradiol made by follicles during OC use,” he said.

In another study that compared follicular suppression by means of manipulation of the hormone-free interval with three different OC regimens, women receiving supplementation with 5 days of 10 mcg ethinyl estradiol had fewer and smaller follicles than women who had a 7-day hormone-free interval.

“I believe that my data add to Endrikat's hypothesis, that OCs that result in better follicular suppression can help women achieve better bleeding profiles,” Dr. Kaunitz said.

MINNEAPOLIS — A newer extended-regimen oral contraceptive that includes 7 days of low-dose estrogen rather than a week of placebo pills is associated with an improved bleeding pattern.

The newer formulation, known as Seasonique, was shown in a cross-study analysis of two phase III trials to be associated with fewer scheduled bleeding days and a reduction in breakthrough bleeding, compared with an older formulation called Seasonale, Dr. Andrew N. Kaunitz said at the annual meeting of the Association of Reproductive Health Professionals.

Both regimens include 84 days of 30 mcg ethinyl estradiol and 150 mcg of levonorgestrel, but Seasonique substitutes 7 days of 10 mcg ethinyl estradiol monotherapy for the 7 days of placebo in the Seasonale regimen. The two drugs are manufactured by Duramed Pharmaceuticals, and Dr. Kaunitz is a speaker or consultant for Duramed Pharmaceuticals and various others.

In the first of the two pivotal 1-year trials, 682 patients from 47 sites throughout the United States were randomized to receive Seasonale or the conventional 28-day oral contraceptive (OC) Nordette, which contains the same daily dose of hormones. The incidence of unscheduled bleeding initially was higher among patients on the extended-cycle regimen, but decreased throughout the study, said Dr. Kaunitz of the University of Florida, Jacksonville, who was one of the investigators in this trial.

By the end of the trial, the incidence of unscheduled bleeding in the extended-cycle regimen was comparable, at a median of 3.6% of days, to that in the conventional group, at 2.9% of days.

In the second study, Seasonique was evaluated in an open-label fashion among 1,006 women being treated at 36 U.S. sites. In this study, the median number of days of unscheduled bleeding in the first extended cycle was similar to that reported in the first trial, but decreased sharply in subsequent cycles. By cycle four, the median number of days of unscheduled bleeding was 0.3 on a per-patient-month basis.

Analysis of the data from these two studies showed that unscheduled bleeding and spotting decreased more quickly with the 91-day regimen that included low-dose estrogen, approaching significance in the second cycle and achieving significance in the third cycle, Dr. Kaunitz said.

Moreover, there were consistent differences in length of scheduled withdrawal bleeding episodes, with a median of 3 days for Seasonique and 4 days for Seasonale, he said.

“This was not a head-to-head study,” he cautioned. Nonetheless, the patient populations were comparable in baseline characteristics, race, age, prior OC use, smoking, and body mass index, and the pattern of unscheduled bleeding seen during the first 3-month cycle was identical across the two studies. Only after the first placebo or low-dose estrogen week was there a difference in bleeding pattern, so observations across the two studies should be valid, he said.

Previous research has found that there is a correlation between the amount of breakthrough bleeding and both higher endogenous 17-β estradiol levels and larger follicle size.

In a meta-analysis of seven prospective trials of various combination OC formulations, the pills that were associated with greater follicular suppression were also those that had improved bleeding profiles.

“Endrikat in Germany [lead author of this meta-analysis] speculated that a biologic mechanism explaining why better follicular suppression was associated with less intermenstrual bleeding might be that the endometrium of women on the pill is not only responsive to exogenous estrogen, as we traditionally thought, but also to the endogenous 17-β estradiol made by follicles during OC use,” he said.

In another study that compared follicular suppression by means of manipulation of the hormone-free interval with three different OC regimens, women receiving supplementation with 5 days of 10 mcg ethinyl estradiol had fewer and smaller follicles than women who had a 7-day hormone-free interval.

“I believe that my data add to Endrikat's hypothesis, that OCs that result in better follicular suppression can help women achieve better bleeding profiles,” Dr. Kaunitz said.

NEW YORK – A new treatment paradigm for benign prostatic hyperplasia is on the horizon, according to Dr. Herbert Lepor.

During the past 2 decades, there has been a shift in the management of benign prostatic hyperplasia (BPH) away from surgery and toward earlier medical intervention, but standard treatment with the α₁-adrenergic receptor antagonists and the 5α-reductase inhibitors leaves a significant cohort of nonresponders, Dr. Lepor said at a meeting on adult and pediatric urology sponsored by New York University.

Among the limitations for β-blockers are safety concerns in patients with low blood pressure and orthostatic hypotension. The α-reductase inhibitors also have a slow onset of action and undesirable side effects, including erectile dysfunction.

Moreover, compliance with daily regimens has been low, at 50% with the α-reductase inhibitors and 67% with the β-blockers, Dr. Lepor said.

A new approach to the medical management of lower urinary tract symptoms (LUTS) secondary to BPH involves using a gonadotropin-releasing hormone (GnRH) antagonist such as cetrorelix. Unlike the GnRH agonists that are commonly used for prostate cancer, GnRH antagonists lower serum testosterone only partially and in a dose-dependent manner.

The goal of using the GnRH antagonist is to reach a level of androgen suppression that will shrink the prostate and improve clinical symptoms without the side effects associated with complete testosterone suppression, explained Dr. Lepor, who is professor and Martin Spatz chairman of the department of urology at the university.

In phase II studies evaluating various doses, regimens, and two different formulations of cetrorelix, statistically significant differences from baseline and compared with placebo were seen on the primary end point of International Prostate Symptom Score (IPSS) at week 12.

In one of these trials, 140 patients were randomized to receive cetrorelix acetate in four doses of 5 mg or 10 mg at 7-day intervals, two doses of 10 mg at 14-day intervals, or placebo.

“Even by week 4, there was a trend toward improvement in symptoms,” Dr. Lepor said. “In patients taking the active drug, there were improvements on IPSS of three to four symptom units, which is equivalent to, if not greater than, the results seen in the best of the β-blocker studies.”

Moreover, flow rates improved rapidly with a response “far greater than anything we see with medical therapy,” he said.

The mean baseline flow rate was about 9 ng/mL, and it increased to about 13 ng/mL in the patients in the active treatment groups.

With regard to prostate size, the results were not significant, although there was a trend to decrease in prostate volume. Testosterone levels during the 4-week injection period showed decreases of about 25%. After the last injection, testosterone levels promptly returned to baseline, and there was no effect on erectile function.

A second phase II trial randomized 250 patients to placebo or cetrorelix pamoate in two doses of 30 mg, three doses of 30 mg, one dose of 60 mg followed by another of 30 mg, or 60 mg followed by 60 mg. All of the doses were given at 14-day intervals.

The results were similar to those in seen in the previous trial, with statistically significant dose-related improvements reported on the IPSS and on urinary flow rates, and with responses persisting out to 120 days. In none of the groups were castration-level testosterone suppression or associated adverse effects seen, Dr. Lepor said.

In a recent review of GnRH antagonists for BPH, Dr. Lepor wrote, “The fact that an intermediate level of testosterone suppression can achieve prostate volume reduction without causing hot flashes, erectile dysfunction, and other adverse events associated with castrate levels of testosterone suggests that there are different androgen thresholds mediating these events. Another possible explanation may be that cetrorelix mediates prostate volume reduction via its effects on other hormones and growth factors” (Rev. Urol. 2006;8:183-9).

Compliance has not been a problem in the clinical trials thus far, with patients having two to three long-lasting treatments a year, he said.

Dr. Lepor, the principal investigator for the phase III trial, disclosed that he serves as a consultant to Æterna Zentaris Inc., the study sponsor.

NEW YORK – A new treatment paradigm for benign prostatic hyperplasia is on the horizon, according to Dr. Herbert Lepor.

During the past 2 decades, there has been a shift in the management of benign prostatic hyperplasia (BPH) away from surgery and toward earlier medical intervention, but standard treatment with the α₁-adrenergic receptor antagonists and the 5α-reductase inhibitors leaves a significant cohort of nonresponders, Dr. Lepor said at a meeting on adult and pediatric urology sponsored by New York University.

Among the limitations for β-blockers are safety concerns in patients with low blood pressure and orthostatic hypotension. The α-reductase inhibitors also have a slow onset of action and undesirable side effects, including erectile dysfunction.

Moreover, compliance with daily regimens has been low, at 50% with the α-reductase inhibitors and 67% with the β-blockers, Dr. Lepor said.

A new approach to the medical management of lower urinary tract symptoms (LUTS) secondary to BPH involves using a gonadotropin-releasing hormone (GnRH) antagonist such as cetrorelix. Unlike the GnRH agonists that are commonly used for prostate cancer, GnRH antagonists lower serum testosterone only partially and in a dose-dependent manner.

The goal of using the GnRH antagonist is to reach a level of androgen suppression that will shrink the prostate and improve clinical symptoms without the side effects associated with complete testosterone suppression, explained Dr. Lepor, who is professor and Martin Spatz chairman of the department of urology at the university.

In phase II studies evaluating various doses, regimens, and two different formulations of cetrorelix, statistically significant differences from baseline and compared with placebo were seen on the primary end point of International Prostate Symptom Score (IPSS) at week 12.

In one of these trials, 140 patients were randomized to receive cetrorelix acetate in four doses of 5 mg or 10 mg at 7-day intervals, two doses of 10 mg at 14-day intervals, or placebo.

“Even by week 4, there was a trend toward improvement in symptoms,” Dr. Lepor said. “In patients taking the active drug, there were improvements on IPSS of three to four symptom units, which is equivalent to, if not greater than, the results seen in the best of the β-blocker studies.”

Moreover, flow rates improved rapidly with a response “far greater than anything we see with medical therapy,” he said.

The mean baseline flow rate was about 9 ng/mL, and it increased to about 13 ng/mL in the patients in the active treatment groups.

With regard to prostate size, the results were not significant, although there was a trend to decrease in prostate volume. Testosterone levels during the 4-week injection period showed decreases of about 25%. After the last injection, testosterone levels promptly returned to baseline, and there was no effect on erectile function.

A second phase II trial randomized 250 patients to placebo or cetrorelix pamoate in two doses of 30 mg, three doses of 30 mg, one dose of 60 mg followed by another of 30 mg, or 60 mg followed by 60 mg. All of the doses were given at 14-day intervals.

The results were similar to those in seen in the previous trial, with statistically significant dose-related improvements reported on the IPSS and on urinary flow rates, and with responses persisting out to 120 days. In none of the groups were castration-level testosterone suppression or associated adverse effects seen, Dr. Lepor said.

In a recent review of GnRH antagonists for BPH, Dr. Lepor wrote, “The fact that an intermediate level of testosterone suppression can achieve prostate volume reduction without causing hot flashes, erectile dysfunction, and other adverse events associated with castrate levels of testosterone suggests that there are different androgen thresholds mediating these events. Another possible explanation may be that cetrorelix mediates prostate volume reduction via its effects on other hormones and growth factors” (Rev. Urol. 2006;8:183-9).

Compliance has not been a problem in the clinical trials thus far, with patients having two to three long-lasting treatments a year, he said.

Dr. Lepor, the principal investigator for the phase III trial, disclosed that he serves as a consultant to Æterna Zentaris Inc., the study sponsor.

NEW YORK – A new treatment paradigm for benign prostatic hyperplasia is on the horizon, according to Dr. Herbert Lepor.

During the past 2 decades, there has been a shift in the management of benign prostatic hyperplasia (BPH) away from surgery and toward earlier medical intervention, but standard treatment with the α₁-adrenergic receptor antagonists and the 5α-reductase inhibitors leaves a significant cohort of nonresponders, Dr. Lepor said at a meeting on adult and pediatric urology sponsored by New York University.

Among the limitations for β-blockers are safety concerns in patients with low blood pressure and orthostatic hypotension. The α-reductase inhibitors also have a slow onset of action and undesirable side effects, including erectile dysfunction.

Moreover, compliance with daily regimens has been low, at 50% with the α-reductase inhibitors and 67% with the β-blockers, Dr. Lepor said.

A new approach to the medical management of lower urinary tract symptoms (LUTS) secondary to BPH involves using a gonadotropin-releasing hormone (GnRH) antagonist such as cetrorelix. Unlike the GnRH agonists that are commonly used for prostate cancer, GnRH antagonists lower serum testosterone only partially and in a dose-dependent manner.

The goal of using the GnRH antagonist is to reach a level of androgen suppression that will shrink the prostate and improve clinical symptoms without the side effects associated with complete testosterone suppression, explained Dr. Lepor, who is professor and Martin Spatz chairman of the department of urology at the university.

In phase II studies evaluating various doses, regimens, and two different formulations of cetrorelix, statistically significant differences from baseline and compared with placebo were seen on the primary end point of International Prostate Symptom Score (IPSS) at week 12.

In one of these trials, 140 patients were randomized to receive cetrorelix acetate in four doses of 5 mg or 10 mg at 7-day intervals, two doses of 10 mg at 14-day intervals, or placebo.

“Even by week 4, there was a trend toward improvement in symptoms,” Dr. Lepor said. “In patients taking the active drug, there were improvements on IPSS of three to four symptom units, which is equivalent to, if not greater than, the results seen in the best of the β-blocker studies.”

Moreover, flow rates improved rapidly with a response “far greater than anything we see with medical therapy,” he said.

The mean baseline flow rate was about 9 ng/mL, and it increased to about 13 ng/mL in the patients in the active treatment groups.

With regard to prostate size, the results were not significant, although there was a trend to decrease in prostate volume. Testosterone levels during the 4-week injection period showed decreases of about 25%. After the last injection, testosterone levels promptly returned to baseline, and there was no effect on erectile function.

A second phase II trial randomized 250 patients to placebo or cetrorelix pamoate in two doses of 30 mg, three doses of 30 mg, one dose of 60 mg followed by another of 30 mg, or 60 mg followed by 60 mg. All of the doses were given at 14-day intervals.

The results were similar to those in seen in the previous trial, with statistically significant dose-related improvements reported on the IPSS and on urinary flow rates, and with responses persisting out to 120 days. In none of the groups were castration-level testosterone suppression or associated adverse effects seen, Dr. Lepor said.

In a recent review of GnRH antagonists for BPH, Dr. Lepor wrote, “The fact that an intermediate level of testosterone suppression can achieve prostate volume reduction without causing hot flashes, erectile dysfunction, and other adverse events associated with castrate levels of testosterone suggests that there are different androgen thresholds mediating these events. Another possible explanation may be that cetrorelix mediates prostate volume reduction via its effects on other hormones and growth factors” (Rev. Urol. 2006;8:183-9).

Compliance has not been a problem in the clinical trials thus far, with patients having two to three long-lasting treatments a year, he said.

Dr. Lepor, the principal investigator for the phase III trial, disclosed that he serves as a consultant to Æterna Zentaris Inc., the study sponsor.

MINNEAPOLIS — Chlamydia trachomatis was not the cause of chronic endometritis in a new study of women using depot-medroxyprogesterone acetate, a finding that holds implications for treatment of endometritis, reported Dr. Andrea R. Thurman.

C. trachomatis is recognized as a cause of breakthrough bleeding—an occurrence often associated with chronic endometritis—among women using oral contraceptive pills.

About 70% of women using depot-medroxyprogesterone acetate (DMPA) also experience breakthrough bleeding during the first year, and a considerable number discontinue the contraceptive.

To determine if C. trachomatis is implicated in the breakthrough bleeding among DMPA users, a cross-sectional study compared endometrial biopsies from 20 women with bleeding and 20 women who were amenorrheic, Dr. Thurman wrote in a poster session at the annual meeting of the Association of Reproductive Health Professionals.

The most common histologic finding on the biopsies was chronic endometritis, which was defined as two plasma cells per endometrial sample, according to Dr. Thurman of the department of obstetrics and gynecology, University of Texas Health Sciences Center, San Antonio.

Chronic endometritis was the histologic diagnosis in 25% of the 40 participating women, and was seen in 35% of women experiencing breakthrough bleeding, compared with 15% of those without bleeding.

Polymerase chain reaction technology then was used to identify C. trachomatis in paraffin-embedded endometrial biopsy tissue sections. Only one patient in each group was infected, and neither of these two patients had chronic endometritis as their histologic diagnosis, Dr. Thurman said.

Despite the fact that the study population was predominantly African American, young, and medically indigent—all risk factors for C. trachomatis infection—there was no correlation between C. trachomatis infection and chronic endometritis in this group.

This finding suggests that chronic endometritis in DMPA users reflects an inflammatory state relating to endometrial atrophy, and supports the use of nonsteroidal anti-inflammatory drugs, rather than antimicrobials or hormonal medication, for treatment, she wrote.

MINNEAPOLIS — Chlamydia trachomatis was not the cause of chronic endometritis in a new study of women using depot-medroxyprogesterone acetate, a finding that holds implications for treatment of endometritis, reported Dr. Andrea R. Thurman.

C. trachomatis is recognized as a cause of breakthrough bleeding—an occurrence often associated with chronic endometritis—among women using oral contraceptive pills.

About 70% of women using depot-medroxyprogesterone acetate (DMPA) also experience breakthrough bleeding during the first year, and a considerable number discontinue the contraceptive.

To determine if C. trachomatis is implicated in the breakthrough bleeding among DMPA users, a cross-sectional study compared endometrial biopsies from 20 women with bleeding and 20 women who were amenorrheic, Dr. Thurman wrote in a poster session at the annual meeting of the Association of Reproductive Health Professionals.

The most common histologic finding on the biopsies was chronic endometritis, which was defined as two plasma cells per endometrial sample, according to Dr. Thurman of the department of obstetrics and gynecology, University of Texas Health Sciences Center, San Antonio.

Chronic endometritis was the histologic diagnosis in 25% of the 40 participating women, and was seen in 35% of women experiencing breakthrough bleeding, compared with 15% of those without bleeding.

Polymerase chain reaction technology then was used to identify C. trachomatis in paraffin-embedded endometrial biopsy tissue sections. Only one patient in each group was infected, and neither of these two patients had chronic endometritis as their histologic diagnosis, Dr. Thurman said.

Despite the fact that the study population was predominantly African American, young, and medically indigent—all risk factors for C. trachomatis infection—there was no correlation between C. trachomatis infection and chronic endometritis in this group.

This finding suggests that chronic endometritis in DMPA users reflects an inflammatory state relating to endometrial atrophy, and supports the use of nonsteroidal anti-inflammatory drugs, rather than antimicrobials or hormonal medication, for treatment, she wrote.

MINNEAPOLIS — Chlamydia trachomatis was not the cause of chronic endometritis in a new study of women using depot-medroxyprogesterone acetate, a finding that holds implications for treatment of endometritis, reported Dr. Andrea R. Thurman.

C. trachomatis is recognized as a cause of breakthrough bleeding—an occurrence often associated with chronic endometritis—among women using oral contraceptive pills.

About 70% of women using depot-medroxyprogesterone acetate (DMPA) also experience breakthrough bleeding during the first year, and a considerable number discontinue the contraceptive.

To determine if C. trachomatis is implicated in the breakthrough bleeding among DMPA users, a cross-sectional study compared endometrial biopsies from 20 women with bleeding and 20 women who were amenorrheic, Dr. Thurman wrote in a poster session at the annual meeting of the Association of Reproductive Health Professionals.

The most common histologic finding on the biopsies was chronic endometritis, which was defined as two plasma cells per endometrial sample, according to Dr. Thurman of the department of obstetrics and gynecology, University of Texas Health Sciences Center, San Antonio.

Chronic endometritis was the histologic diagnosis in 25% of the 40 participating women, and was seen in 35% of women experiencing breakthrough bleeding, compared with 15% of those without bleeding.

Polymerase chain reaction technology then was used to identify C. trachomatis in paraffin-embedded endometrial biopsy tissue sections. Only one patient in each group was infected, and neither of these two patients had chronic endometritis as their histologic diagnosis, Dr. Thurman said.

Despite the fact that the study population was predominantly African American, young, and medically indigent—all risk factors for C. trachomatis infection—there was no correlation between C. trachomatis infection and chronic endometritis in this group.

This finding suggests that chronic endometritis in DMPA users reflects an inflammatory state relating to endometrial atrophy, and supports the use of nonsteroidal anti-inflammatory drugs, rather than antimicrobials or hormonal medication, for treatment, she wrote.

BOSTON — Treatment options for children with juvenile idiopathic arthritis might soon expand, with safety and efficacy now having been demonstrated for two additional biologic agents—even in patients who have failed to respond to methotrexate or another biologic, Dr. Daniel J. Lovell reported at the annual meeting of the American College of Rheumatology.

The sole biologic approved for use in juvenile idiopathic arthritis (JIA) is the tumor necrosis factor (TNF) blocker etanercept, but not all patients respond to this drug. Randomized studies now have shown benefits for the T-cell costimulation modulator abatacept and for another anti-TNF agent, adalimumab. Both of these drugs have been studied and used extensively in adults with rheumatoid arthritis, with approval for use in JIA pending from the Food and Drug Administration, Dr. Lovell said.

The phase III abatacept study included 190 patients who had previously failed other therapies, including methotrexate, etanercept, and anakinra.

“This was the first study in which we enrolled kids who had already received a biologic. They had exhausted our current therapies but still had active disease,” said Dr. Lovell, who is associate director, division of rheumatology, Cincinnati Children's Hospital Medical Center, and professor of pediatrics, University of Cincinnati.

All patients initially received the drug as intravenous infusions of 10 mg/kg on days 1 and 15, and every 28 days thereafter in an open-label fashion for 4 months. They also were permitted to receive methotrexate in doses of 10–30 mg/m

By the end of the open-label phase, the overall ACR pediatric 30 response rate was 65%, while the response rate among those who had previously failed on a biologic agent was 40%.

A total of 123 patients who achieved an ACR pediatric 30 response during the open-label phase were then invited to enter the double-blind portion of the trial; 122 did so.

In this phase of the study, patients were randomized to continue on the active drug or placebo for up to 6 months or until their JIA flared. As soon as patients flared they were placed on the active drug. JIA flared in 53% of patients in the placebo group and 20% of those in the active treatment group.

During the open-label phase of the study, six patients reported serious adverse events, three relating to the underlying disease. During the double-blind phase, no serious adverse events were reported in the abatacept group, and three were seen in the placebo group. Overall, the most common adverse events were influenza, bacteriuria, nasopharyngitis, upper respiratory tract infection, and pyrexia. The safety was similar to that seen with other biologics.

The adalimumab study was a phase III double-blind trial that included 171 patients ranging in age from 4 to 17 years. “A unique aspect of this trial was that we enrolled patients who were already on methotrexate as well as patients who were earlier in the course of disease and had not yet received methotrexate. This was done at the request of the Food and Drug Administration, and the results showed efficacy in both combination and methotrexate-naive groups, he said.

Patients first entered an open-label phase during which they received 24 mg/m

At week 16, 84% of patients had achieved an ACR pediatric 30 response, 77% achieved an ACR pediatric 50 response, 58% achieved an ACR pediatric 70 response, and 27% achieved an ACR pediatric 90 response.

Those who achieved at least an ACR pediatric 30 response were then randomized to continue adalimumab or placebo for 32 weeks or until disease flared. At week 48, ACR pediatric 30, 50, and 70 responses were achieved by 60%, 59%, and 56% of patients in the adalimumab group, respectively, compared with 35%, 35%, and 28% of patients in the placebo group.

The ACR pediatric responses represent a comprehensive picture of disease activity and impact, Dr. Lovell said in a press conference at the meeting. For an ACR pediatric 30 response, a 30% improvement must be seen in three of six core disease parameters such as physician and parent global assessment and number of joints with active arthritis, and there can be a worsening of no more than 30% in one component.

“We found that if patients demonstrated a 30% response and remained at that level, their outcome was dramatically improved, compared with children who didn't reach that level of response,” he said.

Decisions on approval for the two drugs are expected in the first quarter of 2008. Dr. Lovell disclosed that he has received consulting fees from Bristol-Myers Squibb Co. and Abbott Laboratories.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Treatment options for children with juvenile idiopathic arthritis might soon expand, with safety and efficacy now having been demonstrated for two additional biologic agents—even in patients who have failed to respond to methotrexate or another biologic, Dr. Daniel J. Lovell reported at the annual meeting of the American College of Rheumatology.

The sole biologic approved for use in juvenile idiopathic arthritis (JIA) is the tumor necrosis factor (TNF) blocker etanercept, but not all patients respond to this drug. Randomized studies now have shown benefits for the T-cell costimulation modulator abatacept and for another anti-TNF agent, adalimumab. Both of these drugs have been studied and used extensively in adults with rheumatoid arthritis, with approval for use in JIA pending from the Food and Drug Administration, Dr. Lovell said.

The phase III abatacept study included 190 patients who had previously failed other therapies, including methotrexate, etanercept, and anakinra.

“This was the first study in which we enrolled kids who had already received a biologic. They had exhausted our current therapies but still had active disease,” said Dr. Lovell, who is associate director, division of rheumatology, Cincinnati Children's Hospital Medical Center, and professor of pediatrics, University of Cincinnati.

All patients initially received the drug as intravenous infusions of 10 mg/kg on days 1 and 15, and every 28 days thereafter in an open-label fashion for 4 months. They also were permitted to receive methotrexate in doses of 10–30 mg/m

By the end of the open-label phase, the overall ACR pediatric 30 response rate was 65%, while the response rate among those who had previously failed on a biologic agent was 40%.

A total of 123 patients who achieved an ACR pediatric 30 response during the open-label phase were then invited to enter the double-blind portion of the trial; 122 did so.

In this phase of the study, patients were randomized to continue on the active drug or placebo for up to 6 months or until their JIA flared. As soon as patients flared they were placed on the active drug. JIA flared in 53% of patients in the placebo group and 20% of those in the active treatment group.

During the open-label phase of the study, six patients reported serious adverse events, three relating to the underlying disease. During the double-blind phase, no serious adverse events were reported in the abatacept group, and three were seen in the placebo group. Overall, the most common adverse events were influenza, bacteriuria, nasopharyngitis, upper respiratory tract infection, and pyrexia. The safety was similar to that seen with other biologics.

The adalimumab study was a phase III double-blind trial that included 171 patients ranging in age from 4 to 17 years. “A unique aspect of this trial was that we enrolled patients who were already on methotrexate as well as patients who were earlier in the course of disease and had not yet received methotrexate. This was done at the request of the Food and Drug Administration, and the results showed efficacy in both combination and methotrexate-naive groups, he said.

Patients first entered an open-label phase during which they received 24 mg/m

At week 16, 84% of patients had achieved an ACR pediatric 30 response, 77% achieved an ACR pediatric 50 response, 58% achieved an ACR pediatric 70 response, and 27% achieved an ACR pediatric 90 response.

Those who achieved at least an ACR pediatric 30 response were then randomized to continue adalimumab or placebo for 32 weeks or until disease flared. At week 48, ACR pediatric 30, 50, and 70 responses were achieved by 60%, 59%, and 56% of patients in the adalimumab group, respectively, compared with 35%, 35%, and 28% of patients in the placebo group.

The ACR pediatric responses represent a comprehensive picture of disease activity and impact, Dr. Lovell said in a press conference at the meeting. For an ACR pediatric 30 response, a 30% improvement must be seen in three of six core disease parameters such as physician and parent global assessment and number of joints with active arthritis, and there can be a worsening of no more than 30% in one component.

“We found that if patients demonstrated a 30% response and remained at that level, their outcome was dramatically improved, compared with children who didn't reach that level of response,” he said.

Decisions on approval for the two drugs are expected in the first quarter of 2008. Dr. Lovell disclosed that he has received consulting fees from Bristol-Myers Squibb Co. and Abbott Laboratories.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Treatment options for children with juvenile idiopathic arthritis might soon expand, with safety and efficacy now having been demonstrated for two additional biologic agents—even in patients who have failed to respond to methotrexate or another biologic, Dr. Daniel J. Lovell reported at the annual meeting of the American College of Rheumatology.

The sole biologic approved for use in juvenile idiopathic arthritis (JIA) is the tumor necrosis factor (TNF) blocker etanercept, but not all patients respond to this drug. Randomized studies now have shown benefits for the T-cell costimulation modulator abatacept and for another anti-TNF agent, adalimumab. Both of these drugs have been studied and used extensively in adults with rheumatoid arthritis, with approval for use in JIA pending from the Food and Drug Administration, Dr. Lovell said.

The phase III abatacept study included 190 patients who had previously failed other therapies, including methotrexate, etanercept, and anakinra.

“This was the first study in which we enrolled kids who had already received a biologic. They had exhausted our current therapies but still had active disease,” said Dr. Lovell, who is associate director, division of rheumatology, Cincinnati Children's Hospital Medical Center, and professor of pediatrics, University of Cincinnati.

All patients initially received the drug as intravenous infusions of 10 mg/kg on days 1 and 15, and every 28 days thereafter in an open-label fashion for 4 months. They also were permitted to receive methotrexate in doses of 10–30 mg/m

By the end of the open-label phase, the overall ACR pediatric 30 response rate was 65%, while the response rate among those who had previously failed on a biologic agent was 40%.

A total of 123 patients who achieved an ACR pediatric 30 response during the open-label phase were then invited to enter the double-blind portion of the trial; 122 did so.

In this phase of the study, patients were randomized to continue on the active drug or placebo for up to 6 months or until their JIA flared. As soon as patients flared they were placed on the active drug. JIA flared in 53% of patients in the placebo group and 20% of those in the active treatment group.

During the open-label phase of the study, six patients reported serious adverse events, three relating to the underlying disease. During the double-blind phase, no serious adverse events were reported in the abatacept group, and three were seen in the placebo group. Overall, the most common adverse events were influenza, bacteriuria, nasopharyngitis, upper respiratory tract infection, and pyrexia. The safety was similar to that seen with other biologics.

The adalimumab study was a phase III double-blind trial that included 171 patients ranging in age from 4 to 17 years. “A unique aspect of this trial was that we enrolled patients who were already on methotrexate as well as patients who were earlier in the course of disease and had not yet received methotrexate. This was done at the request of the Food and Drug Administration, and the results showed efficacy in both combination and methotrexate-naive groups, he said.

Patients first entered an open-label phase during which they received 24 mg/m

At week 16, 84% of patients had achieved an ACR pediatric 30 response, 77% achieved an ACR pediatric 50 response, 58% achieved an ACR pediatric 70 response, and 27% achieved an ACR pediatric 90 response.

Those who achieved at least an ACR pediatric 30 response were then randomized to continue adalimumab or placebo for 32 weeks or until disease flared. At week 48, ACR pediatric 30, 50, and 70 responses were achieved by 60%, 59%, and 56% of patients in the adalimumab group, respectively, compared with 35%, 35%, and 28% of patients in the placebo group.

The ACR pediatric responses represent a comprehensive picture of disease activity and impact, Dr. Lovell said in a press conference at the meeting. For an ACR pediatric 30 response, a 30% improvement must be seen in three of six core disease parameters such as physician and parent global assessment and number of joints with active arthritis, and there can be a worsening of no more than 30% in one component.

“We found that if patients demonstrated a 30% response and remained at that level, their outcome was dramatically improved, compared with children who didn't reach that level of response,” he said.

Decisions on approval for the two drugs are expected in the first quarter of 2008. Dr. Lovell disclosed that he has received consulting fees from Bristol-Myers Squibb Co. and Abbott Laboratories.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

VIENNA — Treatment with methyl aminolevulinate-photodynamic therapy was as effective as surgery for superficial basal cell carcinoma, Dr. Rolf-Markus Szeimies reported in a poster session at the 16th Congress of the European Academy of Dermatology and Venereology.

Among the methods for removal of basal cell carcinomas are simple excision, Mohs surgery, radiotherapy, curettage/electrodessication, and cryosurgery, with the choice of treatment depending on type, size, depth, and location of the lesion.

Methyl aminolevulinate-photodynamic therapy (MAL-PDT) has previously been shown to be as effective as cryotherapy for removal of these lesions and to have superior cosmetic results. Now, in the first multicenter randomized trial comparing MAL-PDT with simple excision, similar findings have been found, according to Dr. Szeimies of the department of dermatology, Regensburg (Germany) University Hospital.

A total of 196 patients whose mean age was 63.8 years were included in the study. The mean number of lesions per patient was 1.4, and the mean diameter of the lesions was 12.4 mm.

Patients randomized to MAL-PDT underwent two treatment sessions 7 days apart, with the option of repeat treatment at 3 months if clinical response was incomplete. Those randomized to surgery underwent simple elliptical excision with 3-mm margins from the estimated edge of the lesion.

The lesion complete response rate was 87% with MAL-PDT and 89% with excision, confirming the noninferiority of MAL-PDT to surgery, wrote Dr. Szeimies.

Results were similar in the two groups for lesions on the trunk and neck, with MAL-PDT and excision having complete response rates of 85% and 89%, respectively. For lesions on the face and scalp, MAL-PDT and excision showed complete response rates of 95% and 67%.

Complete response was not related to size of the lesion.

Investigator-rated cosmetic outcome favored MAL-PDT, with 87% of lesions having good to excellent outcome, compared with 58% of those in the surgery group.

Patients also preferred the cosmetic outcome with MAL-PDT, with 93% rating the outcome as good to excellent, compared with 81% of the patients in the excision group.

The study was sponsored by Galderma, which makes the MAL-PDT used in the study.

In a recent review of experience with MAL-PDT for basal cell carcinoma, Dr. Szeimies noted that, while surgery remains the preferred method of treatment, some patients—such as those with large lesions, poor vasculature, and concomitant use of anticoagulants or immunosuppressives—may be poor candidates for surgery.

Moreover, postsurgical keloid or dystrophic scarring is common, particularly on the trunk. "Because of the relatively low-risk nature of superficial [basal cell carcinoma], scarring problems should be taken into consideration when choosing a suitable therapy. Therefore, PDT may offer significant advantages over surgical or other destructive techniques" he wrote (Dermatol. Clin. 2007;25:89–94).

Dr. Szeimies disclosed no conflicts of interest.

VIENNA — Treatment with methyl aminolevulinate-photodynamic therapy was as effective as surgery for superficial basal cell carcinoma, Dr. Rolf-Markus Szeimies reported in a poster session at the 16th Congress of the European Academy of Dermatology and Venereology.

Among the methods for removal of basal cell carcinomas are simple excision, Mohs surgery, radiotherapy, curettage/electrodessication, and cryosurgery, with the choice of treatment depending on type, size, depth, and location of the lesion.

Methyl aminolevulinate-photodynamic therapy (MAL-PDT) has previously been shown to be as effective as cryotherapy for removal of these lesions and to have superior cosmetic results. Now, in the first multicenter randomized trial comparing MAL-PDT with simple excision, similar findings have been found, according to Dr. Szeimies of the department of dermatology, Regensburg (Germany) University Hospital.

A total of 196 patients whose mean age was 63.8 years were included in the study. The mean number of lesions per patient was 1.4, and the mean diameter of the lesions was 12.4 mm.

Patients randomized to MAL-PDT underwent two treatment sessions 7 days apart, with the option of repeat treatment at 3 months if clinical response was incomplete. Those randomized to surgery underwent simple elliptical excision with 3-mm margins from the estimated edge of the lesion.

The lesion complete response rate was 87% with MAL-PDT and 89% with excision, confirming the noninferiority of MAL-PDT to surgery, wrote Dr. Szeimies.

Results were similar in the two groups for lesions on the trunk and neck, with MAL-PDT and excision having complete response rates of 85% and 89%, respectively. For lesions on the face and scalp, MAL-PDT and excision showed complete response rates of 95% and 67%.

Complete response was not related to size of the lesion.

Investigator-rated cosmetic outcome favored MAL-PDT, with 87% of lesions having good to excellent outcome, compared with 58% of those in the surgery group.

Patients also preferred the cosmetic outcome with MAL-PDT, with 93% rating the outcome as good to excellent, compared with 81% of the patients in the excision group.

The study was sponsored by Galderma, which makes the MAL-PDT used in the study.

In a recent review of experience with MAL-PDT for basal cell carcinoma, Dr. Szeimies noted that, while surgery remains the preferred method of treatment, some patients—such as those with large lesions, poor vasculature, and concomitant use of anticoagulants or immunosuppressives—may be poor candidates for surgery.

Moreover, postsurgical keloid or dystrophic scarring is common, particularly on the trunk. "Because of the relatively low-risk nature of superficial [basal cell carcinoma], scarring problems should be taken into consideration when choosing a suitable therapy. Therefore, PDT may offer significant advantages over surgical or other destructive techniques" he wrote (Dermatol. Clin. 2007;25:89–94).

Dr. Szeimies disclosed no conflicts of interest.

VIENNA — Treatment with methyl aminolevulinate-photodynamic therapy was as effective as surgery for superficial basal cell carcinoma, Dr. Rolf-Markus Szeimies reported in a poster session at the 16th Congress of the European Academy of Dermatology and Venereology.

Among the methods for removal of basal cell carcinomas are simple excision, Mohs surgery, radiotherapy, curettage/electrodessication, and cryosurgery, with the choice of treatment depending on type, size, depth, and location of the lesion.

Methyl aminolevulinate-photodynamic therapy (MAL-PDT) has previously been shown to be as effective as cryotherapy for removal of these lesions and to have superior cosmetic results. Now, in the first multicenter randomized trial comparing MAL-PDT with simple excision, similar findings have been found, according to Dr. Szeimies of the department of dermatology, Regensburg (Germany) University Hospital.

A total of 196 patients whose mean age was 63.8 years were included in the study. The mean number of lesions per patient was 1.4, and the mean diameter of the lesions was 12.4 mm.

Patients randomized to MAL-PDT underwent two treatment sessions 7 days apart, with the option of repeat treatment at 3 months if clinical response was incomplete. Those randomized to surgery underwent simple elliptical excision with 3-mm margins from the estimated edge of the lesion.

The lesion complete response rate was 87% with MAL-PDT and 89% with excision, confirming the noninferiority of MAL-PDT to surgery, wrote Dr. Szeimies.

Results were similar in the two groups for lesions on the trunk and neck, with MAL-PDT and excision having complete response rates of 85% and 89%, respectively. For lesions on the face and scalp, MAL-PDT and excision showed complete response rates of 95% and 67%.

Complete response was not related to size of the lesion.

Investigator-rated cosmetic outcome favored MAL-PDT, with 87% of lesions having good to excellent outcome, compared with 58% of those in the surgery group.

Patients also preferred the cosmetic outcome with MAL-PDT, with 93% rating the outcome as good to excellent, compared with 81% of the patients in the excision group.

The study was sponsored by Galderma, which makes the MAL-PDT used in the study.

In a recent review of experience with MAL-PDT for basal cell carcinoma, Dr. Szeimies noted that, while surgery remains the preferred method of treatment, some patients—such as those with large lesions, poor vasculature, and concomitant use of anticoagulants or immunosuppressives—may be poor candidates for surgery.

Moreover, postsurgical keloid or dystrophic scarring is common, particularly on the trunk. "Because of the relatively low-risk nature of superficial [basal cell carcinoma], scarring problems should be taken into consideration when choosing a suitable therapy. Therefore, PDT may offer significant advantages over surgical or other destructive techniques" he wrote (Dermatol. Clin. 2007;25:89–94).

Dr. Szeimies disclosed no conflicts of interest.

BOSTON – Increased rheumatoid arthritis disease activity is associated with a greater risk of developing infections, judging from the analysis of data from a large rheumatology database, Dr. Daniel E. Furst said at the annual meeting of the American College of Rheumatology.

In clinical trials and in clinical practice, infectious adverse events are common among patients with rheumatoid arthritis (RA), and the frequency may vary according to factors that include disease activity and drug therapies, said Dr. Furst, who is Carl M. Pearson Professor of Medicine and director of arthritis clinical research at the University of California, Los Angeles.

To investigate the relationship between infections and disease activity after adjustment for the effects of drug therapy, analyses on infection rates were done for RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) database who were on stable doses of disease-modifying antirheumatic drugs, biologic agents, or corticosteroids, according to Dr. Furst.

Two composite measures of disease activity were used in the analysis: the Clinical Disease Activity Index (CDAI) among the entire cohort of 3,782 patients, and the Disease Activity Score (DAS) 28 among the subset of 2,081 patients who also had erythrocyte sedimentation rate (ESR) values available within 2 weeks of the study visit.

The CDAI is a validated measure that is calculated as the sum of the swollen joint count, tender joint count, patient global assessment on a 10-cm visual analog scale (VAS), and evaluator global assessment also on a 10-cm VAS.

Initial analysis considered the influence of age, sex, education, race, body mass index, disease duration, insurance, work status, smoking history, and RA drug therapies.

Covariates that were found to be significantly associated with disease activity or infection then were analyzed using a generalized estimating equation for Poisson regression multivariate model with infection as the dependent variable, and incident rate ratios (IRR) were calculated.

A total of 1,160 infections were seen among the entire cohort during 3,653 patient-years. The IRR was found to be significant for disease activity on both CDAI and DAS28.

Age, female sex, and work status-disabled also were significant, though less so, on at least one measure. An IRR of 1.04 for CDAI represents a 4% increase in risk per 5-unit increase in CDAI score, Dr. Furst explained.

No other significant associations were seen, including current use of tumor necrosis factor blockers, disease-modifying antirheumatic drug, or corticosteroids.

“In this cohort of RA patients from the CORRONA database who were on stable background medications, increased disease activity was associated with a higher probability of developing infection,” Dr. Furst wrote in a poster session. Other factors, such as age and sex, also may affect the incidence, although further investigation is needed to clarify this.

Higher disease activity might be associated with an increased risk of infection because of subtle dysfunction of the immune system, particularly the innate immune system, though this remains speculative at the moment, Dr. Furst said in an interview. “There is increasing information that there is a connection between the innate and adaptive immune systems in RA and it is the innate immune system that responds initially to infection.

“The study suggests rheumatologists should be aggressive about controlling RA and that, contrary to previous dogma, aggressive treatment actually may decrease infections despite the broader use of therapies that theoretically could worsen infections because of their immunosuppressive effects,” he said. “This will require careful follow-up and management and a balancing act between the side effects of drugs and their positive effects.”

Dr. Furst said he has received research grants and consulting fees from numerous pharmaceutical firms.

'Contrary to previous dogma, aggressive treatment actually may decrease infections.' DR. FURST

BOSTON – Increased rheumatoid arthritis disease activity is associated with a greater risk of developing infections, judging from the analysis of data from a large rheumatology database, Dr. Daniel E. Furst said at the annual meeting of the American College of Rheumatology.

In clinical trials and in clinical practice, infectious adverse events are common among patients with rheumatoid arthritis (RA), and the frequency may vary according to factors that include disease activity and drug therapies, said Dr. Furst, who is Carl M. Pearson Professor of Medicine and director of arthritis clinical research at the University of California, Los Angeles.

To investigate the relationship between infections and disease activity after adjustment for the effects of drug therapy, analyses on infection rates were done for RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) database who were on stable doses of disease-modifying antirheumatic drugs, biologic agents, or corticosteroids, according to Dr. Furst.

Two composite measures of disease activity were used in the analysis: the Clinical Disease Activity Index (CDAI) among the entire cohort of 3,782 patients, and the Disease Activity Score (DAS) 28 among the subset of 2,081 patients who also had erythrocyte sedimentation rate (ESR) values available within 2 weeks of the study visit.

The CDAI is a validated measure that is calculated as the sum of the swollen joint count, tender joint count, patient global assessment on a 10-cm visual analog scale (VAS), and evaluator global assessment also on a 10-cm VAS.

Initial analysis considered the influence of age, sex, education, race, body mass index, disease duration, insurance, work status, smoking history, and RA drug therapies.

Covariates that were found to be significantly associated with disease activity or infection then were analyzed using a generalized estimating equation for Poisson regression multivariate model with infection as the dependent variable, and incident rate ratios (IRR) were calculated.

A total of 1,160 infections were seen among the entire cohort during 3,653 patient-years. The IRR was found to be significant for disease activity on both CDAI and DAS28.

Age, female sex, and work status-disabled also were significant, though less so, on at least one measure. An IRR of 1.04 for CDAI represents a 4% increase in risk per 5-unit increase in CDAI score, Dr. Furst explained.

No other significant associations were seen, including current use of tumor necrosis factor blockers, disease-modifying antirheumatic drug, or corticosteroids.

“In this cohort of RA patients from the CORRONA database who were on stable background medications, increased disease activity was associated with a higher probability of developing infection,” Dr. Furst wrote in a poster session. Other factors, such as age and sex, also may affect the incidence, although further investigation is needed to clarify this.

Higher disease activity might be associated with an increased risk of infection because of subtle dysfunction of the immune system, particularly the innate immune system, though this remains speculative at the moment, Dr. Furst said in an interview. “There is increasing information that there is a connection between the innate and adaptive immune systems in RA and it is the innate immune system that responds initially to infection.

“The study suggests rheumatologists should be aggressive about controlling RA and that, contrary to previous dogma, aggressive treatment actually may decrease infections despite the broader use of therapies that theoretically could worsen infections because of their immunosuppressive effects,” he said. “This will require careful follow-up and management and a balancing act between the side effects of drugs and their positive effects.”

Dr. Furst said he has received research grants and consulting fees from numerous pharmaceutical firms.

'Contrary to previous dogma, aggressive treatment actually may decrease infections.' DR. FURST

BOSTON – Increased rheumatoid arthritis disease activity is associated with a greater risk of developing infections, judging from the analysis of data from a large rheumatology database, Dr. Daniel E. Furst said at the annual meeting of the American College of Rheumatology.

In clinical trials and in clinical practice, infectious adverse events are common among patients with rheumatoid arthritis (RA), and the frequency may vary according to factors that include disease activity and drug therapies, said Dr. Furst, who is Carl M. Pearson Professor of Medicine and director of arthritis clinical research at the University of California, Los Angeles.

To investigate the relationship between infections and disease activity after adjustment for the effects of drug therapy, analyses on infection rates were done for RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) database who were on stable doses of disease-modifying antirheumatic drugs, biologic agents, or corticosteroids, according to Dr. Furst.

Two composite measures of disease activity were used in the analysis: the Clinical Disease Activity Index (CDAI) among the entire cohort of 3,782 patients, and the Disease Activity Score (DAS) 28 among the subset of 2,081 patients who also had erythrocyte sedimentation rate (ESR) values available within 2 weeks of the study visit.

The CDAI is a validated measure that is calculated as the sum of the swollen joint count, tender joint count, patient global assessment on a 10-cm visual analog scale (VAS), and evaluator global assessment also on a 10-cm VAS.

Initial analysis considered the influence of age, sex, education, race, body mass index, disease duration, insurance, work status, smoking history, and RA drug therapies.

Covariates that were found to be significantly associated with disease activity or infection then were analyzed using a generalized estimating equation for Poisson regression multivariate model with infection as the dependent variable, and incident rate ratios (IRR) were calculated.

A total of 1,160 infections were seen among the entire cohort during 3,653 patient-years. The IRR was found to be significant for disease activity on both CDAI and DAS28.

Age, female sex, and work status-disabled also were significant, though less so, on at least one measure. An IRR of 1.04 for CDAI represents a 4% increase in risk per 5-unit increase in CDAI score, Dr. Furst explained.

No other significant associations were seen, including current use of tumor necrosis factor blockers, disease-modifying antirheumatic drug, or corticosteroids.

“In this cohort of RA patients from the CORRONA database who were on stable background medications, increased disease activity was associated with a higher probability of developing infection,” Dr. Furst wrote in a poster session. Other factors, such as age and sex, also may affect the incidence, although further investigation is needed to clarify this.

Higher disease activity might be associated with an increased risk of infection because of subtle dysfunction of the immune system, particularly the innate immune system, though this remains speculative at the moment, Dr. Furst said in an interview. “There is increasing information that there is a connection between the innate and adaptive immune systems in RA and it is the innate immune system that responds initially to infection.

“The study suggests rheumatologists should be aggressive about controlling RA and that, contrary to previous dogma, aggressive treatment actually may decrease infections despite the broader use of therapies that theoretically could worsen infections because of their immunosuppressive effects,” he said. “This will require careful follow-up and management and a balancing act between the side effects of drugs and their positive effects.”

Dr. Furst said he has received research grants and consulting fees from numerous pharmaceutical firms.

'Contrary to previous dogma, aggressive treatment actually may decrease infections.' DR. FURST

MINNEAPOLIS — Sublingually administered misoprostol was significantly more effective than the drug given orally after mifepristone for medical abortion in a prospective randomized trial, Sheila Raghavan said at the annual meeting of the Association of Reproductive Health Professionals.

“Medical abortion is becoming more popular and is preferred by women because of the ease of administration and convenience,” Ms. Raghavan said. Misoprostol typically has been administered orally or vaginally for abortion, although this use is off-label and, in fact, the labeling for misoprostol carries a boxed warning stating that its use by pregnant women can not only cause abortion but also birth defects and uterine rupture.

Pharmacokinetic studies have shown higher bioavailability and more rapid absorption when given sublingually. Initial investigations into this route of administration used high doses of sublingual misoprostol and found a high—98%—efficacy rate, but also showed a high rate of side effects. For example, in one study comparing sublingual and vaginal misoprostol given in a dose of 800 mcg, 54% of women receiving the sublingual drug experienced nausea, compared with 32% of those receiving the drug vaginally (Hum. Reprod. 2003;18:2315–8).

For investigation of whether a lower dose (400 mcg) of misoprostol given sublingually after 200 mg oral mifepristone would be effective, tolerable, and acceptable to women, 480 women who ranged in age from 18 to 46 years who were presenting for termination of intrauterine pregnancy were enrolled in the study. Gestational ages up to 63 days were permitted. Approximately 55% of the women had had previous abortions. The trial took place in Moldova, said Ms. Raghavan, who is program research coordinator at Gynuity Health Projects, a reproductive health research and technical assistance organization in New York City.

A total of 240 women were randomized to receive the oral drug, and 240 to receive the sublingual drug, at home 24 hours after receiving 200 mg oral mifepristone in the clinic. Two weeks later they were seen for follow-up assessment, at which time success rates of 98.7% and 94% were seen in the sublingual and oral groups respectively, a difference that statistically favored the sublingual route, Ms. Raghavan said. Four cases, all in the oral group, required surgical intervention.

Fever and chills occurred more frequently in the sublingual group, with 28% of patients reporting these side effects, compared with 18% in the oral group. The nausea lasted significantly longer in the oral group, however, and more than 80% of women in both groups reported that the side effects were acceptable or very acceptable. More than 91% of women in both groups reported being satisfied or very satisfied with the procedure, she said.

The study demonstrates that sublingual misoprostol in a dose of 400 mcg given after 200 mg mifepristone is more effective and as acceptable to women as the oral regimen in inducing abortion, she concluded.

MINNEAPOLIS — Sublingually administered misoprostol was significantly more effective than the drug given orally after mifepristone for medical abortion in a prospective randomized trial, Sheila Raghavan said at the annual meeting of the Association of Reproductive Health Professionals.

“Medical abortion is becoming more popular and is preferred by women because of the ease of administration and convenience,” Ms. Raghavan said. Misoprostol typically has been administered orally or vaginally for abortion, although this use is off-label and, in fact, the labeling for misoprostol carries a boxed warning stating that its use by pregnant women can not only cause abortion but also birth defects and uterine rupture.

Pharmacokinetic studies have shown higher bioavailability and more rapid absorption when given sublingually. Initial investigations into this route of administration used high doses of sublingual misoprostol and found a high—98%—efficacy rate, but also showed a high rate of side effects. For example, in one study comparing sublingual and vaginal misoprostol given in a dose of 800 mcg, 54% of women receiving the sublingual drug experienced nausea, compared with 32% of those receiving the drug vaginally (Hum. Reprod. 2003;18:2315–8).

For investigation of whether a lower dose (400 mcg) of misoprostol given sublingually after 200 mg oral mifepristone would be effective, tolerable, and acceptable to women, 480 women who ranged in age from 18 to 46 years who were presenting for termination of intrauterine pregnancy were enrolled in the study. Gestational ages up to 63 days were permitted. Approximately 55% of the women had had previous abortions. The trial took place in Moldova, said Ms. Raghavan, who is program research coordinator at Gynuity Health Projects, a reproductive health research and technical assistance organization in New York City.

A total of 240 women were randomized to receive the oral drug, and 240 to receive the sublingual drug, at home 24 hours after receiving 200 mg oral mifepristone in the clinic. Two weeks later they were seen for follow-up assessment, at which time success rates of 98.7% and 94% were seen in the sublingual and oral groups respectively, a difference that statistically favored the sublingual route, Ms. Raghavan said. Four cases, all in the oral group, required surgical intervention.

Fever and chills occurred more frequently in the sublingual group, with 28% of patients reporting these side effects, compared with 18% in the oral group. The nausea lasted significantly longer in the oral group, however, and more than 80% of women in both groups reported that the side effects were acceptable or very acceptable. More than 91% of women in both groups reported being satisfied or very satisfied with the procedure, she said.

The study demonstrates that sublingual misoprostol in a dose of 400 mcg given after 200 mg mifepristone is more effective and as acceptable to women as the oral regimen in inducing abortion, she concluded.

MINNEAPOLIS — Sublingually administered misoprostol was significantly more effective than the drug given orally after mifepristone for medical abortion in a prospective randomized trial, Sheila Raghavan said at the annual meeting of the Association of Reproductive Health Professionals.

“Medical abortion is becoming more popular and is preferred by women because of the ease of administration and convenience,” Ms. Raghavan said. Misoprostol typically has been administered orally or vaginally for abortion, although this use is off-label and, in fact, the labeling for misoprostol carries a boxed warning stating that its use by pregnant women can not only cause abortion but also birth defects and uterine rupture.

Pharmacokinetic studies have shown higher bioavailability and more rapid absorption when given sublingually. Initial investigations into this route of administration used high doses of sublingual misoprostol and found a high—98%—efficacy rate, but also showed a high rate of side effects. For example, in one study comparing sublingual and vaginal misoprostol given in a dose of 800 mcg, 54% of women receiving the sublingual drug experienced nausea, compared with 32% of those receiving the drug vaginally (Hum. Reprod. 2003;18:2315–8).

For investigation of whether a lower dose (400 mcg) of misoprostol given sublingually after 200 mg oral mifepristone would be effective, tolerable, and acceptable to women, 480 women who ranged in age from 18 to 46 years who were presenting for termination of intrauterine pregnancy were enrolled in the study. Gestational ages up to 63 days were permitted. Approximately 55% of the women had had previous abortions. The trial took place in Moldova, said Ms. Raghavan, who is program research coordinator at Gynuity Health Projects, a reproductive health research and technical assistance organization in New York City.

A total of 240 women were randomized to receive the oral drug, and 240 to receive the sublingual drug, at home 24 hours after receiving 200 mg oral mifepristone in the clinic. Two weeks later they were seen for follow-up assessment, at which time success rates of 98.7% and 94% were seen in the sublingual and oral groups respectively, a difference that statistically favored the sublingual route, Ms. Raghavan said. Four cases, all in the oral group, required surgical intervention.

Fever and chills occurred more frequently in the sublingual group, with 28% of patients reporting these side effects, compared with 18% in the oral group. The nausea lasted significantly longer in the oral group, however, and more than 80% of women in both groups reported that the side effects were acceptable or very acceptable. More than 91% of women in both groups reported being satisfied or very satisfied with the procedure, she said.

The study demonstrates that sublingual misoprostol in a dose of 400 mcg given after 200 mg mifepristone is more effective and as acceptable to women as the oral regimen in inducing abortion, she concluded.