Background Certolizumab pegol (CZP) is a PEGylated, Fc-free anti-TNF approved in several countries for the treatment of rheumatoid arthritis (RA) and Crohn’s disease (CD). Pre-clinical and clinical data suggest a lack of active neonatal Fc receptor-dependent placental transfer of CZP.1,2
Objectives To provide additional information on the primary pregnancy outcomes for women exposed to CZP through a retrospective safety database analysis.
Methods The UCB Pharma global safety database was searched for all medically confirmed cases of pregnancy, including both clinical trial and post-marketing reports, through March 6, 2012. The proportion of live births, miscarriages and elective terminations for women directly exposed to CZP (maternal exposure) before and during pregnancy was examined. Exposure to concomitant medications (pooled across indications) and disease activity prior to conception was reviewed for pregnancies that occurred in clinical trial subjects (N=57).
Results Of 294 reported pregnancies, 152 had known outcomes; of which 139 occurred following maternal exposure to CZP. For these pregnancies, the underlying conditions for the pregnant mothers were CD (109/139), RA (17/139) and healthy subjects (2/139); indication was unknown/unavailable for the remaining pregnancies. 91/139 (66%) pregnancies were from the US. 103/139 (74%) pregnancies resulted in live births and the median gestational age was 38 weeks (data available for 40 births). 21/139 (15%) pregnancies ended in miscarriage and 15/139 (11%) women had an elective termination. In the 103 live births there were 2 (1.4%) cases of congenital disorder (US general population rate is 3%3). A single neonatal death was reported, however medical review showed no evidence of correlation with CZP exposure. Where data was available from clinical trial subjects, corticosteroids (7/29 live births, 2/10 miscarriages, 3/13 elective terminations) and methotrexate (2/29 live births, 2/10 miscarriages, 1/13 elective terminations) were the most common relevant concomitant medications reported during pregnancy. However, exposure to concomitant medication was either brief (<3 weeks) or unknown (medication end date unknown) therefore conclusions are limited. Most clinical trial subjects had low to moderate disease activity at conception (median CDAI 184.9 for 22 CD subjects, DAS28(ESR) range 1.1-6.1 for 7 RA subjects); however, as subjects exited clinical trial at conception further data are unavailable. Miscarriages were not associated with high disease activity at conception. Conclusions regarding concomitant medications and disease activity are limited due to low numbers.
Conclusions Currently available data from pregnant women exposed to CZP reported outcomes similar to what is expected in the general population (US General Population4: 64% live births, 17% miscarriages and 19% elective terminations; data from 6,390,000 pregnancies). However, additional data from large numbers of pregnant women exposed to CZP are required to fully evaluate the safety and tolerability of CZP in pregnancy.
Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.
Disclosure of Interest M. Clowse Consultant for: UCB Pharma, D. Wolf Grant/research support from: Abbott, BMS, Genetech, GIVEN Imaging, Janssen, Millennium, Prometheus, UCB Pharma, Consultant for: Abbott, Genetech, GIVEN Imaging, Janssen, Millennium, Prometheus, Salix, UCB Pharma, Speakers bureau: Abbott, Janssen, Prometheus, Salix, UCB Pharma, Warner Chilcott, F. Förger Consultant for: Roche, UCB Pharma, Speakers bureau: Roche, UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, G. Kosutic Shareholder of: UCB Pharma, Employee of: UCB Pharma, S. Williams Shareholder of: UCB Pharma, Employee of: UCB Pharma, I. Terpstra Employee of: UCB Pharma, U. Mahadevan Grant/research support from: Prometheus, Millenium, GSK, Consultant for: Abbott, Janssen, Elan, Genetech, Shire, UCB Pharma