Do Pre-Pregnancy Biologic DMARDs Increase the Risk of Birth Defects?

SAN FRANCISCO, CA—In women with long-standing rheumatic disease there was "no significantly increased risk of malformations or other harmful consequences" in those "exposed to biologic disease-modifying antirheumatic drugs (bDMARDs) before or at conception," results of a study reported at the 2015 ACR/ARHP Annual Meeting have found.

However, "within this limited sample of pregnancies a remaining risk cannot be ruled out entirely," reported lead study author Anja Strangfeld, MD, German Rheumatism Research Centre, Berlin, Germany, and coauthors.

In contrast, "disease activity increased during pregnancy in a considerable proportion of patients."

Citing a widespread but unproven “assumption of spontaneous remission among pregnant women with rheumatoid arthritis” and observational data suggesting that bDMARDs can be safely used “until conception, but [that] the impact of bDMARD treatment during pregnancy is unclear,” the researchers studied pregnancy outcomes and disease activity among women who were administered bDMARDs prior to conception.

"We descriptively analyzed all pregnancies and their outcomes that were reported to the German biologics register RABBIT until end of 2014,” Dr. Strangfeld reported. Of 1,981 female patients with rheumatoid arthritis 45 years of age or younger, 106 pregnancies in 88 patients were reported. The investigators conducted "additional telephone interviews with a focus on the course of pregnancy, disease activity, and treatment during pregnancy" with a subgroup of 64 patients with pregnancies reported to 2011.

Of the 106 pregnancies, 11 were bDMARD-naive, 38 had stopped the bDMARD prior to conception, and 57 were exposed to bDMARDs at the time of conception.

Among those who stopped, they had received their last bDMARD infusion or injection at least 4 weeks (rituximab 6 months) before conception; 12 had received etanercept, 9 adalimumab, 2 tocilizumab, 2 infliximab, and 13 rituximab.

Of those exposed to bDMARDS, 29 received etanercept, 11 adalimumab, 5 tocilizumab, 4 certolizumab pegol, 3 rituximab, 3 abatacept, 1 infliximab, and 1 golimumab.

"Before conception, 23 patients were in remission, and 10 of them (43%) remained in remission during pregnancy," Dr. Strangfeld reported. "Of the 49 patients not in remission before conception, only 7 (14%) reached remission during pregnancy."

Differences in spontaneous abortion rates between treatment regimens did not reach statistical significance; none occurred in those not exposed to bDMARDs, 5 (13%) in those who stopped bDMARDs before conception, and 11 (19%) in those exposed to bDMARDs. 

No malformations or anomalies were observed in the bDMARD-naive group. In those who stopped bDMARDs, one children had anal atresia born to a mother exposed to adalimumab until 4 weeks prior to conception. One child had congenital nystagmus after a preterm birth to a mother who had stopped adalimumab more than 6 months before conception. One induced abortion followed diagnosis of a child with trisomia 21; the mother was 38 years of age and had stopped rituximab treatment more than 8 months prior to conception. A case of spina bifida was detected in one child whose mother had stopped etanercept more than 9 months prior to conception.

Among women exposed to bDMARDs, one child was diagnosed with talipes; the mother was taking adalimumab and also has talipes. 

In the subsample of patients the investigators interviewed, higher disease activity was observed in women with premature births. Among the 55 women with mature births, patient-reported global health (with 0 being "good" and 10 being "very poor") was 3.6, compared with 5.4 for those who had preterm singleton births.

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