Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy

Ghalandari, Nafise; Kemper, Erik; Crijns, Ineke; Wolbink, Gertjan; Rispens, Theo; Smeele, H. T.; Dolhain, Radboud J E M

doi:10.1136/annrheumdis-2021-221036

Cited by 19 publications

(18 citation statements)

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“…Etanercept is known to cross the placental barrier, being detected in the serum of children born from patients treated with etanercept during pregnancy (Berthelsen et al, 2010). However, a recent studied reported that etanercept was not detectable in cord blood sample, whereas others TNF-α inhibitors were detectable, including adalimumab and infliximab (Ghalandari et al, 2021). Therefore, one possibility is that TNFα inhibition may be impacting on placentation.…”

Section: Discussionmentioning

confidence: 99%

Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats’ Pregnancy

et al. 2022

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Etanercept is a tumor necrosis factor alpha (TNF-α) inhibitor chronically used to treat autoimmune diseases. However, the use of etanercept during pregnancy still needs to be further investigated. The aim of this study is to evaluate the etanercept treatment during pregnancy, analyzing maternal reproductive performance, fetal outcomes, and placental repercussions. Wistar rats (200–250 g) were mated and randomly distributed into two experimental groups: control and etanercept (n = 10 animals/group). Treatments with etanercept (0.8 mg/kg, s.c.), or saline (control group) were carried out on days 0, 6, 12, and 18 of gestation. On the morning of the 21st day of pregnancy, rats were euthanized in a CO2 chamber and submitted to laparotomy to remove the fetuses, placentas, ovaries, and maternal organs. There were no differences between groups in the following parameters: water and food consumption; placental efficiency; reproductive parameters, including number of corpora lutea and implants, reabsorption, and pre- and post-implantation losses. However, etanercept treatment increased liver weight, reduced fetal and placental weight, decreased the placental junction zone, reduced the percentage of normal fetuses, and increased visceral or skeletal fetal abnormalities. Therefore, etanercept resulted in damages more related to fetus and placenta. However, more studies with different doses are required to better predict possible injuries elicited using etanercept during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats’ Pregnancy

et al. 2022

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“…6 , 7 , 8 , 9 Among these, CZP crosses the placenta in very scarce amounts due to the lack of the Fc part. 10 Data from more than 500 prospectively followed pregnancies exposed to CZP did not indicate higher rates of congenital malformations (CMs) compared to the general population. CZP is generally considered to be safe for use during pregnancy.…”

Section: Introductionmentioning

confidence: 96%

Reported congenital malformations after exposure to non‐tumour necrosis factor inhibitor biologics: A retrospective comparative study in EudraVigilance

Ghalandari

Crijns

Bergman

et al. 2022

Brit J Clinical Pharma

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Funding information Dutch Medicines Evaluation Board (College ter Beoordeling van Geneesmiddelen; CBG-MEB)Aims: To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitor biologics (non-TNFi biologics) compared to certolizumab pegol (CZP).Methods: A retrospective comparative study was conducted in the EudraVigilance (EV) database. A safe biologic (CZP) was considered as the reference group. Odds ratios (ORs) for CMs were calculated for each non-TNFi biologic (including abatacept, anakinra, belimumab, ixekizumab, rituximab, secukinumab, tocilizumab, ustekinumab and vedolizumab), versus CZP (quantitative assessment). Then, CM patterns were reviewed in consultation with a clinical geneticist (qualitative assessment).Results: ORs were not statistically significant except for belimumab and vedolizumab (similar in magnitude). Except for vedolizumab, no specific CM patterns were observed for the included non-TNFi biologics. Three cases of corpus callosum agenesis (CCA) were identified for vedolizumab (versus none in CZP and other investigated non-TNFi biologics). Two of the CCA cases were associated with other neurological CMs (one cerebral ventriculomegaly with microcephaly and one polymicrogyria). This may indicate that these CCAs are related to undiagnosed genetic alterations or are associated with the underlying maternal disease, although a definite relationship with vedolizumab exposure cannot be ruled out. Conclusion: No special safety signal was identified regarding the occurrence of CMs after exposure to abatacept (n = 64), anakinra (n = 20), belimumab (n = 93), ixekizumab (n = 29), rituximab (n = 57), secukinumab (n = 128), tocilizumab (n = 124) and ustekinumab (n = 215). Regarding observed CCAs in the vedolizumab group (n = 113), no firm conclusions can be made based on available information.

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“…The last American College of Rheumatology (ACR) guidelines are in line with those issued by the EULAR [ 14 ]. It was subsequently confirmed that discontinuing TNFi treatment at the recommended time points resulted in undetectable or low cord blood levels of TNFi [ 24 ]. Furthermore, no signal for adverse pregnancy outcomes or congenital malformations was observed in CZP-exposed pregnancies documented in a large post-marketing pharmacovigilance database [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase®)

et al. 2022

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Introduction Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited. Objective The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases. Methods We performed a disproportionality analysis of the World Health Organization’s VigiBase ® pharmacovigilance database from 1968 to June 1, 2021. Data were collected in June 2021. By using terms for different hierarchical levels of the Medical Dictionary for Regulatory Activities, we selected the following fetal or neonatal ADRs: stillbirth, premature birth, low birth weight, small for gestational age, and congenital malformations. The frequency of all identified ADRs for biologics of interest (adalimumab, infliximab, golimumab, certolizumab, etanercept, anakinra, canakinumab, tocilizumab, sarilumab, ustekinumab, guselkumab, secukinumab, ixekizumab, belimumab, abatacept, and rituximab) was compared with that of all other reports for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval]. Reports with known concomitant use of teratogenic drugs were excluded from the main analysis. Other analyses included ROR stratifications by therapeutic indication in the periods 1968–2021 and 2001–2021, and an analysis after excluding reports with steroids. Results In the main analysis, the RORs were particularly high for musculoskeletal malformations with anakinra (7.18 [3.50–14.73]), canakinumab (19.54 [12.82–29.79]), and abatacept (5.09 [2.77–9.33]), and for immune system disorders with canakinumab (347.88 [217.9–555.50]) and rituximab (9.27 [2.95–29.15]). After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75–141.25]). Conclusion We identified possible associations with some adverse fetal and neonatal outcomes, suggesting that vigilance is required when prescribing certain biologics during pregnancy. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00564-4.

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Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy

Cited by 19 publications

References 13 publications

Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats’ Pregnancy

Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats’ Pregnancy

Reported congenital malformations after exposure to non‐tumour necrosis factor inhibitor biologics: A retrospective comparative study in EudraVigilance

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase®)

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