Study Probes Safety of Biologics in Pregnancy

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

The OTIS Study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment of pregnant women began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500, explained Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. After birth, the infants are followed for up to a year.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. While the literature contains case reports, the OTIS Project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared to 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percent of live births was higher in those treated with etanercept compared with those with similar rheumatic diseases (92% vs. 85%) and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%). Taking the drug did not seem to be related to the average birth weight in full-term infants.

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” she said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%).

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups versus healthy controls (4%). Mean birth weight was approximately 300 grams less in full term infants whose mothers had received adalimumab compared with healthy controls but similar to full-term infants in the disease-matched comparison group. Rates of major malformations were similar (4%–5%) in all groups.

“Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis,” she said.

Most of the malformations were isolated, and no patterns of birth defect were apparent.

Source DR. CHAMBERS

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

The OTIS Study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment of pregnant women began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500, explained Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. After birth, the infants are followed for up to a year.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. While the literature contains case reports, the OTIS Project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared to 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percent of live births was higher in those treated with etanercept compared with those with similar rheumatic diseases (92% vs. 85%) and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%). Taking the drug did not seem to be related to the average birth weight in full-term infants.

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” she said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%).

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups versus healthy controls (4%). Mean birth weight was approximately 300 grams less in full term infants whose mothers had received adalimumab compared with healthy controls but similar to full-term infants in the disease-matched comparison group. Rates of major malformations were similar (4%–5%) in all groups.

“Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis,” she said.

Most of the malformations were isolated, and no patterns of birth defect were apparent.

Source DR. CHAMBERS

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

The OTIS Study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment of pregnant women began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500, explained Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. After birth, the infants are followed for up to a year.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. While the literature contains case reports, the OTIS Project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared to 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percent of live births was higher in those treated with etanercept compared with those with similar rheumatic diseases (92% vs. 85%) and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%). Taking the drug did not seem to be related to the average birth weight in full-term infants.

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” she said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%).

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups versus healthy controls (4%). Mean birth weight was approximately 300 grams less in full term infants whose mothers had received adalimumab compared with healthy controls but similar to full-term infants in the disease-matched comparison group. Rates of major malformations were similar (4%–5%) in all groups.

“Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis,” she said.

Most of the malformations were isolated, and no patterns of birth defect were apparent.

Source DR. CHAMBERS