More and more women are becoming pregnant while on anti–tumor necrosis factor (TNF) biosimilars used to treat inflammatory disorders. However, there is “little data” on the safety and effectiveness of biosimilars in pregnancy, according to authors of a recent retrospective study.
More and more women are becoming pregnant while on anti-tumor necrosis factor (TNF) biosimilars used to treat inflammatory disorders. However, there is “little data” on the safety and effectiveness of biosimilars in pregnancy, according to authors of a recent retrospective study.
The concern is that anti-TNF antibodies could be transferred to the fetus via the placenta, leading to neonatal immune suppression. The authors noted these concerns led to recommendations to discontinue anti-TNF biologics during pregnancy by the British Society of Rheumatology, European League Against Rheumatism, and American College of Rheumatology, although these guidelines do acknowledge anti-TNF biologics can be continued during pregnancy if indicated.
In contrast, the British Society for Gastroenterology and European Crohn’s and Colitis Organization recommend physicians discuss the benefits and risks with patients, but advise continuing anti-TNF treatment in patients with active disease or high risk of relapse. The American Gastroenterological Association recommends continuing anti-TNF therapy during pregnancy.
In light of these inconsistent guidelines, the researchers wrote, “it is important to have some evidence that these drugs can be used with increasing confidence in pregnancy” and allow women “to have more informed conversations about the risks and benefits of continuing biosimilar therapies throughout pregnancy.”
Immunoglobulin G (IgG) antibodies are indeed transported across the placenta throughout pregnancy, and transport of IgG increases linearly during that time. However, negative effects of anti-TNF biologics on infants “have not been substantiated clinically,” the authors wrote, and furthermore meta-analyses on originator TNF inhibitor biologics have supported the safety of these therapies during pregnancy.
Electronic health records from 18 women with inflammatory-mediated immune disorders who were undergoing treatment with TNF inhibitor biosimilars prior to conception were analyzed to assess disease activity, laboratory and clinical data, and pregnancy outcomes.
64% of Women Who Stopped Their Biosimilar Experienced a Flare
The average duration of biologic therapy prior to conception was 5 years (range, 1-12 years) and average time from diagnosis to pregnancy was 10 years (range, 3-18 years). Seven women continued biosimilar therapy throughout pregnancy. Two women stopped treatment during the first trimester, 8 during the second trimester, and 1 during the third trimester.
Disease activity was well-controlled in 15 of the 18 women prior to conception. Flares occurred in 7 of the 11 women who stopped biosimilar treatment (64%) compared to 2 of the 7 who continued biosimilar treatment (29%). The researchers said this finding is consistent with previous evidence that stopping anti-TNF therapy early in pregnancy increases the risk of a flare. Six of the 7 women who experienced flares after stopping the biosimilar restarted biosimilar treatment.
Each of the 18 pregnancies resulted in a live birth, with an average gestation of 39 weeks (range, 36 weeks and 6 days to 41 weeks and 1 day).Seven women had a vaginal delivery, 10 had elective Cesarean sections, and 1 had an emergency Caesarean section. One preterm birth occurred in which the patient was induced due to intrahepatic cholestasis of pregnancy. No congenital abnormalities were observed, and there were no admissions to the neonatal unit.
Women Who Stopped Biosimilar Treatment Delivered Earlier
The researchers observed that women who stopped biosimilar therapy delivered on average at 38 weeks and 5 days compared to 39 weeks and 5 days for those who continued biosimilar treatment. They noted that flares of inflammatory disease during pregnancy have been shown to increase the risk of low birth weight and preterm delivery. Although the cause of the earlier delivery among women who stopped their biosimilar in this study is unknown, they postulate “it may be related to an increase in maternal disease activity precipitating delivery.”
No significant differences were found between women who continued or discontinued biosimilar therapy in birth weight or birth weight centile. The overall average birth weight centile was 34th (range, fourth-99th).
The researchers concluded their findings demonstrate the safety of anti-TNF biosimilar therapy during pregnancy, consistent with the research on originator TNF inhibitors. They wrote, “not only should women on biosimilar therapies feel confident to conceive while using these drugs, but it would appear prudent that continuation of biosimilar [anti-TNF] therapy throughout pregnancy should be the norm rather than the exception to prevent later disease flares.” Because of the small number of patients in their retrospective study, they added, “all conclusions must be supported by future studies and registry data.”
Scott R, Parker H, Mccartney S, Harrow P, Williams D, Giles I. Outcomes following biosimilar TNF inhibitor use for inflammatory-mediated immune disorders in pregnancy. Obstet Med. 2022;15(2):104-107. doi:10.1177/1753495X211028779