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...

BackgroundPrior studies have suggested higher rates of preterm birth in pregnancies to women with rheumatoid arthritis.ObjectivesWe sought to identify differences in the pregnancy outcomes of women with and without RA, and pregnancies that occurred prior to and following RA diagnosis.MethodsA cross-sectional survey was completed by 75 women with RA age-matched to 75 women without RA. Information collected about each prior pregnancy included: pregnancy outcome (spontaneous abortion, stillbirth, elective termination, ectopic pregnancy, or live birth); the timing of delivery; infant anomalies; methotrexate exposure in pregnancy; and whether the pregnancy was planned. Simple statistics were used to compare pregnancy outcomes between women with and without RA and pregnancies prior to and following RA diagnosis.ResultsThe majority of women with RA (83%) and controls (64%) were white, and 11% of women with RA and 28% of controls were African American. About half of controls and 31% of women with RA had education beyond college. The average age at the time of the survey was 32 years (SD: 5) in both RA patients and controls, and the average age at RA diagnosis was 23 years (SD: 10). There were 76 pregnancies in 40 women with RA and 99 pregnancies in 33 healthy controls (see table). The overall rates of live birth, spontaneous abortion, and ectopic pregnancies were similar between groups; there were no stillbirths.The rate of elective termination was significantly different, with 9% of RA and 30% of control pregnancies terminated (p=0.005). The large majority of the terminations in women with RA occurred prior to diagnosis. The higher frequency of unplanned pregnancy among the controls (38% unplanned RA vs 67% unplanned controls, p=0.0002) likely contributed to this higher termination rate. Of unplanned pregnancies, 45% were terminated in controls, 33% in pre-RA pregnancies, and 9% in post-RA pregnancies. No planned pregnancies were terminated. Three pregnancies in women with RA were exposed to methotrexate (2 unplanned, 1 planned) resulting in 2 spontaneous abortions and 1 live birth, born at term without any reported abnormalities.The rates of preterm birth and infant abnormalities did not differ significantly between those with and without RA, though among women with RA, all preterm births and infant abnormalities occurred after RA diagnosis. Each of the RA preterm births was delivered between 31–34 weeks gestation. Preeclampsia was more common in women with RA, but did not differ significantly between pregnancies prior to and after RA diagnosis.A total of 41% of the post-RA pregnancies had an adverse pregnancy outcome (miscarriage, preterm delivery, or infant abnormality), compared to 13% of pre-RA pregnancies (p=0.01) and 20% of control pregnancies (p=0.01).ConclusionsWomen with RA, overall, had similar rates of miscarriage, stillbirth, and ectopic pregnancy compared to healthy women, but pregnancies that occurred after RA diagnosis had higher rates of these adverse outcomes. More pregnancies in women with RA were plan...

BackgroundWomen with active chronic rheumatic inflammatory conditions (RA, PsA, AxSpA) often face uncertainty regarding the safety of the use of biologics during breastfeeding.1 Limited and non-validated data exist on the potential transfer of anti-TNFs into breast milk.2 CRADLE (NCT02154425) was the first sponsored study to evaluate certolizumab pegol (CZP) concentrations in breast milk, and to estimate the Average Daily Infant Dose (ADID) of maternal CZP.ObjectivesTo determine the concentration of CZP in breast milk and calculate the ADID of maternal CZP.MethodsCRADLE was a pharmacokinetic study of lactating mothers (≥6 weeks postpartum) receiving commercial CZP. Decision to treat with CZP and breastfeed was independent of study participation. At steady state (≥3 CZP doses), breast milk samples were collected on Days 0, 2, 4, 6, 8, 10, 12, 14 (±28) from each mother across 1 dosing period. CZP was detected using a highly sensitive, CZP-specific electrochemiluminescence immunoassay validated in milk (lower limit of quantification [LLOQ]=0.032 μg/mL; 10-fold lower than previous assays). CZP stability in milk was confirmed.Results18 CZP-treated mothers were screened: 17 entered the sampling period; 16 on CZP 200 mg Q2W; 1 on CZP 400 mg Q4W (7 RA; 5 SpA; 5 CD; Table A). Samples from 4/17 mothers had no measurable CZP in breast milk; 13/17 had quantifiable levels for at least 1 time point (highest concentration: 0.076 μg/mL; Table B). Estimated ADID ranged 0–0.0104 mg/kg/day; median Relative Infant Dose (RID; calculated post hoc3): 0.15%. Infants of CZP-exposed mothers had a safety profile consisting of events occurring in unexposed infants of similar age.ConclusionsCZP was below the lower limit of quantification in 56% of the milk samples. When detectable, CZP concentrations were less than 3x LLOQ (<1% of expected plasma concentration of a therapeutic dose4), indicating no to minimal transfer of CZP from plasma to breast milk. RID was below 0.5% of maternal dose; <10% is unlikely to be of clinical concern.3 CZP absorption via breast milk is unlikely, due to low bioavailability and its Fc-free molecular structure. These findings support continuation of CZP treatment during breastfeeding.References Götestam Skorpen C. Ann Rheum Dis 2016;75:795–810.Ben-Horin S. J Crohns Colitis 2011;5:555–8.Hale TW. Textbook of Human Lactation. Amarillo, TX: Hale Publishing, 2007.Lacroix BD. Gastroenterology 2010;138:S163–4. AcknowledgementsThis study was funded by UCB Pharma. We are indebted to the mothers and their infants for their altruistic participation. We thank the nurses, investigator teams and Nicole Hurst, PPD, and acknowledge Amanda Golembesky and Gerry Parker, UCB Pharma. Editorial services were provided by Costello Medical Consulting.Disclosure of InterestM. Clowse Grant/research support from: Pfizer, Janssen, Consultant for: UCB Pharma, F. Förger Grant/research support from: UCB Pharma, Speakers bureau: Mepha, Roche, UCB Pharma, C. Hwang Grant/research support from: AbbVie, UCB Pharma, Consultant for: Janssen, J. Thorp Gr...