P0557 - Pharmacovigilance Data on Pregnancy Outcomes in Women With Crohn’s Disease Exposed to Certolizumab Pegol

Sunday, October 24, 2021

3:30 PM – 7:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Marla C. Dubinsky, MD

Icahn School of Medicine at Mount Sinai
New York, NY, United States

Megan E. Clowse, MD¹, Marla C. Dubinsky, MD², Rebecca Fischer-Betz, MD³, Catherine Nelson-Piercy, MD⁴, Angela E. Scheuerle, MD⁵, Brigitte Stephan, MD⁶, Thomas Kumke, MSc⁷, Rachna Kasliwal, MBBS⁸, Bernard Lauwerys, MD⁹, Frauke Förger, MD¹⁰
¹Duke University Medical Center, Durham, NC; ²Icahn School of Medicine at Mount Sinai, New York, NY; ³Heinrich Heine University Düsseldorf, Düsseldorf, Nordrhein-Westfalen, Germany; ⁴Guy’s and St. Thomas’ Hospital, London, England, United Kingdom; ⁵UT Southwestern Medical Center, Dallas, TX; ⁶University Medical Center Hamburg‐Eppendorf, Hamburg, Hamburg, Germany; ⁷UCB Pharma, Monheim am Rhein, Nordrhein-Westfalen, Germany; ⁸UCB Pharma, Slough, England, United Kingdom; ⁹UCB Pharma, Anderlecht, Brussels Hoofdstedelijk Gewest, Belgium; ¹⁰Inselspital, University Hospital and University of Bern, Bern, Bern, Switzerland

Introduction: In women of childbearing age (WoCBA), the link between active Crohn’s disease (CD) and adverse pregnancy outcomes necessitates continued treatment through pregnancy to maintain remission.¹ Tumor necrosis factor inhibitors (TNFi) are commonly used to treat CD, but real-world data on outcomes from TNFi-exposed pregnancies are limited. Certolizumab pegol (CZP), a PEGylated, Fc-free TNFi, has negligible to low placental transfer from mother to infant during the third trimester. We report outcomes from CZP-exposed pregnancies in women with CD and other chronic inflammatory diseases (CID) from the UCB Pharmacovigilance safety database.

Methods: Prospectively reported CZP-exposed pregnancies with known outcomes in women with CID, including CD, which were recorded in the UCB Pharmacovigilance safety database up to 01-Nov-20, were analyzed. Reported pregnancy outcomes: live birth, ectopic pregnancy, pregnancy loss (spontaneous miscarriages and induced abortions), stillbirth, congenital malformations, preterm birth and low birth weight (LBW). Multivariate logistic stepwise regression was performed on the total population of CZP-exposed women with any CID to identify baseline variables associated with pregnancy outcomes.

Results: 1,392 prospective, CZP-exposed pregnancies with known outcomes in women with any CID were analyzed, of which 293 were in women with CD. Rates of live birth and pregnancy loss were 88.4% and 10.5%, respectively, in the total population (Table). In the multivariate analysis, CD and NSAID use were significantly associated with decreased live births and increased pregnancy loss (Figure). Rates of congenital malformations in live births were similar between women with CD (2.8%) and all women with CID (2.4%). Rates of preterm birth and LBW were also comparable between women with CD (9.5% and 8.7%, respectively) and women with CID (9.8% and 8.0%).

Discussion: Despite methodological limitations, no new signal for adverse pregnancy outcomes or congenital malformations was observed in this population of CZP-exposed patients. Multivariate confounders analysis revealed associations between CD and decreased live births and increased pregnancy loss, in line with previous reports.¹ These findings provide further guidance for women with CD receiving CZP who are pregnant or planning a pregnancy, and their treating clinicians.

References: 1. Hashash JG, Kane S. Pregnancy and Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2015;11:96–102.

Figure: Figure. Baseline variables associated with (A) live birth, (B) pregnancy loss, (C) preterm birth and (D) low birth weight from multivariate logistic regression analysis. The following baseline variables were evaluated in the multivariate logistic regression analyses if they included ≥10% of the population and there were patients both with and without the pregnancy outcome in question: maternal age (≤35 years/>35 years); indication for CZP treatment (rheumatoid arthritis, axial spondyloarthritis, Crohn’s disease); concomitant medications (systemic corticosteroids, NSAIDs, methotrexate/leflunomide); and maternal infections. Only variables identified as being significantly associated with the pregnancy outcome of interest are shown (p<0.05 for entry into the multivariate model and p≥0.1 for elimination). [a] Includes spontaneous miscarriages, and elective and medically indicated abortions. CI: confidence interval; CZP: certolizumab pegol; NSAID: non-steroidal anti-inflammatory drug; OR: odds ratio.

	Patients with CD (n=293)	All patients [a] (N=1,392)
*Maternal characteristics*
Maternal age (years), mean (SD)	30.3 (4.8)	31.9 (5.1)
CZP exposure, n/N (%)
In at least the first trimester	234/293 (79.9)	1,021/1,392 (73.3)
In all trimesters	134/293 (45.7)	547/1,392 (39.3)
*Pregnancy outcomes,* *n/N (%)*
Total number of outcomes [b]	299	1,425
Live births	253/299 (84.6)	1,259/1,425 (88.4)
Ectopic pregnancies [c]	1/293 (0.3)	5/1,392 (0.4)
All pregnancy losses	43/299 (14.4)	150/1,425 (10.5)
Miscarriage	33/299 (11.0)	111/1,425 (7.8)
Elective/medically indicated abortion	10/299 (3.3)	39/1,425 (2.7)
Stillbirths	2/299 (0.7)	11/1,425 (0.8)
Preterm birth [d] based on live births	24/253 (9.5)	124/1,259 (9.8)
Low birth weight (< 2.5 kg) based on live births	22/253 (8.7)	101/1,259 (8.0)
Congenital malformations based on all outcomes	8/299 (2.7)	35/1,425 (2.5)
Congenital malformations based on live births	7/253 (2.8)	30/1,259 (2.4)

Table: Table. Pregnancy outcomes following maternal exposure to CZP. [a] All CZP-exposed pregnancies in women with CID, including those with CD; [b] Multiple births are counted as separate outcomes, so the total number of outcomes is higher than the total number of patients/pregnancies; [c] Reported using the total number of patients/pregnancies as the denominator; [d] Delivery before 37 weeks’ gestation. CD: Crohn’s disease; CID: chronic inflammatory disease; CZP: certolizumab pegol; SD: standard deviation.

Disclosures:

Megan Clowse: Janssen – Grant/Research Support. Pfizer – Grant/Research Support. UCB Pharma – Consultant.

Marla Dubinsky: AbbVie – Consultant. Arena – Consultant. BMS – Consultant. Celgene – Consultant. Janssen – Consultant. Pfizer – Consultant. Takeda – Consultant. UCB Pharma – Consultant.

Rebecca Fischer-Betz: AbbVie – Consultant. BMS – Consultant. Celgene – Consultant. Chugai – Consultant. Eli Lilly – Consultant. Janssen – Consultant. Novartis – Consultant. Pfizer – Consultant. Sanofi – Consultant. UCB Pharma – Consultant.

Catherine Nelson-Piercy: Alliance Pharma – Consultant. UCB Pharma – Consultant.

Angela Scheuerle: Antiretroviral Pregnancy Registry – Consultant. Harmony Biosciences – Consultant. ICON – Consultant. IQVIA – Consultant. NovoNordisk – Consultant. PPD – Consultant. Roche – Consultant. Sanofi-Genzyme – Consultant. Syneos – Consultant. UCB Pharma – Consultant. ViiV – Consultant.

Brigitte Stephan: AbbVie – Consultant. UCB Pharma – Consultant.

Thomas Kumke: UCB Pharma – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Rachna Kasliwal: UCB Pharma – Employee.

Bernard Lauwerys: UCB Pharma – Employee.

Frauke Förger: Mepha – Speaker's Bureau. Roche – Speaker's Bureau. UCB Pharma – Grant/Research Support, Speaker's Bureau.

Megan E. Clowse, MD¹, Marla C. Dubinsky, MD², Rebecca Fischer-Betz, MD³, Catherine Nelson-Piercy, MD⁴, Angela E. Scheuerle, MD⁵, Brigitte Stephan, MD⁶, Thomas Kumke, MSc⁷, Rachna Kasliwal, MBBS⁸, Bernard Lauwerys, MD⁹, Frauke Förger, MD¹⁰. P0557 - Pharmacovigilance Data on Pregnancy Outcomes in Women With Crohn’s Disease Exposed to Certolizumab Pegol, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.