The use of certolizumab pegol during pregnancy does not appear to be associated with an increased risk of fetal death or congenital malformations, according to results of a new study.

Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.

There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.

Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.

The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.

Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).

In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.

“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.

Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.

Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.

“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”

The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.

“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”

However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.

“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.

The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.

SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.

Reassurance for women taking certolizumab during pregnancy