Pregnancy Outcomes After Exposure to Certolizumab Pegol

Abstract

ObjectiveAnti–tumor necrosis factor (anti‐TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti‐TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc‐free anti‐TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.MethodsProspective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.ResultsOf 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.ConclusionThis analysis represents the largest cohort of pregnant women exposed to an anti‐TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

“…Therefore, the one reported case of major CM for certolizumab pegol in this study could not be associated with the described cases [ 40 ]. Nine described cases in other articles could be linked to certolizumab pegol and were as follows (the rest of the cases were not described explicitly or could not be linked to this specific biologic): Clubfeet and Hirschsprung’s disease ( n = 1) Anal fistula ( n = 1) Talipes ( n = 1) Vesicoureteric reflux ( n = 1) Cerebral ventricle dilatation ( n = 1) Hydronephrosis ( n = 1) Congenital heart disease ( n = 1) Accessory auricle ( n = 1) Polydactyly ( n = 1) [ 75 , 78 ]. …”

“…Two cases of neonatal deaths occurred in a twin pregnancy; one of the twins was born at 25th GW with brain damage and pneumo-peritoneum, the other twin was born at 27th GW with heart defects and passed away due to a gastrointestinal infection at the 8th week of age [ 78 ].…”

Pharmacovigilance of Biopharmaceuticals in Rheumatic Diseases, Adverse Events, Evolution, and Perspective: An Overview

“…The AE for tocilizumab were renal pielectasis, oesophageal fistula, cardiovascular malformations, and alterations in the development of the central nervous system (CNS), as well as reports of abortion [ 172 , 173 ]. In the case of certolizumab, the AE reported were abortion, in addition to accessory atrium, anal fistula, hydrocephalus, macrosomia, and polydactyly in neonates [ 174 ]. In infants, cetolizumab pegol is associated with respiratory infections, gastroesophageal reflux, and lichen striatus as AE, while in mothers, breast abscesses, respiratory infections, and headaches were reported [ 175 ].…”

Immunosuppressives and biologics during pregnancy and lactation

“…A most recently published evaluation of a safety database comprised prospectively accumulated data on more than 500 pregnancies, in which CZP was applied and the outcomes of which were known. In turn, resulting in no aggravated risk of CM, this analysis represents the largest cohort of women treated with an anti-TNF-α antibody during pregnancy [67]. …”