OP0067 Pregnancy Outcomes after Exposure to Certolizumab Pegol: Updated Results from Safety Surveillance

Abstract

Background Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF approved in 45 countries for the treatment of rheumatoid arthritis (RA) and/or Crohn's disease (CD); it was recently approved by the EMA for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Analysis of pregnancy data from the UCB Pharma global safety database through 06 March 2012 has been published previously.1 Objectives To provide an updated analysis of pregnancy outcomes in rheumatic patients (pts) after CZP exposure, with a focus on RA, by including new reports and pregnancies that were still ongoing at the time of the last retrospective analysis. Methods The UCB Pharma global safety database, designed to house and report adverse events for UCB Pharma products, was searched for all medically confirmed cases of pregnancy through 28 March 2013. Reported pregnancies included women who became pregnant while participating in a clinical study and spontaneous post-marketing reports. The number of live births, spontaneous miscarriages and elective terminations for neonates exposed to CZP (maternal and paternal exposure) was examined. Congenital abnormalities, neonatal deaths and maternal demographics were also investigated. Results As of 28 March 2013, 309 CZP exposed pregnancies were reported: 285 were maternal exposure, 24 were paternal. For pregnancies with maternal exposure, although the major underlying condition was CD (190/285), RA was the underlying condition for 52 of the 285 women with the remaining 43/285 encompassing other indications, including axSpA and PsA. Pregnancy outcomes were available for 190 of these 285 pregnancies: 42 in women with RA, 124 in women with CD and 24 in women with other rheumatic indications. For the 42 pregnancies in women with RA with known outcomes, whether spontaneously reported or within a clinical trial context, 26 (61.9%) resulted in live birth, 9 (21.4%) in spontaneous miscarriage and 7 (16.7%) in elective termination. The Table presents characteristics for pregnancies in women with RA compared to those for all reported maternal exposure pregnancies. Five congenital anomalies were reported, in four neonates, among all live births with maternal CZP exposure (n=132): vesicoureteric reflux, congenital morbus hirschsprung disease and club foot, right aortic arch with aberrant left subclavian artery, and mild unilateral hydronephrosis on antenatal ultrasound (described as healthy upon birth). None of these events were considered related to CZP by the treating physicians. A single neonatal death was reported after maternal exposure in one of a set of twins delivered before 26 weeks of gestation. Conclusions Updated analysis of pregnancy outcomes after exposure to CZP supports previous reports suggesting no apparent impact of maternal CZP exposure on pregnancy outcomes. Additional prospective data are required to fully evaluate the safety and tolerability of CZP in pregnancy. References Clowse M. Arthritis Rheum 2012; 64(Suppl10):S702 Acknowledgements The authors acknowledge Co...

Pregnancy, Periods, and “The Pill”: Exploring the Reproductive Experiences of Women with Inflammatory Arthritis

“…However, users of these medications trended toward a greater likelihood of reporting that a physician had told them not to have (more) children (23% vs 12% of nonusers) or were more likely to express concerns about the effects of their medications on a developing fetus (71% vs 55% of nonusers). TNF‐alpha inhibitors are currently considered to be compatible with pregnancy .…”

FRI0066 Behavior of the multi-biomarker disease activity (vectra da algorithm) score and components in patients with rheumatoid arthritis treated with tocilizumab

“…Clowse и соавт. [30]. Он содержал обновленный анализ результатов по беременности при ревма-тических заболеваниях на фоне лечения ЦЗП, с акцентом на РА.…”

Editorial: Safety of Tumor Necrosis Factor Inhibitors in Pregnancy

“…That study also found an even higher rate of birth defects in babies born to women with chronic inflammatory diseases exposed to a TNFi agent than in babies born to women with chronic inflammatory diseases not receiving a TNFi agent (6.3% versus 4.7%), but the difference was not significant . The study of CZP by Clowse et al had a very low rate of congenital abnormalities (1.7%), but there was no comparison group and the thoroughness of the reporting is variable compared to a population study .…”

“…However, the findings provide reassurance that many pregnancies have been exposed to CZP, and where results are known, there is no clear signal of fetal harm. The study by Clowse et al does raise many issues of interpretation of maternal drug exposure in rheumatic diseases such as RA . The generalizability of these findings to other TNFi agents is unknown, partially because of the lack of late active placental transfer of CZP due to its unique structure .…”

“…In this issue of Arthritis & Rheumatology , Clowse et al present an updated analysis of a pharmacovigilance database of outcomes of pregnancies with certolizumab pegol (CZP) exposure . Outcomes of interest were live births, miscarriages, abortions, stillbirths, and congenital malformations.…”