P2C309: Clinical Outcomes of Standard of Care for Early-onset Severe Hemolytic Disease of the Fetus and Newborn (EOS-HDFN)

Saturday, October 21, 2023

12:00 PM – 1:30 PM US EDT

Location: Walter E. Washington Convention Center, Exhibit Hall A

Background: Standard of care (SOC) for pregnancies at risk of EOS-HDFN includes noninvasive monitoring for fetal anemia and intrauterine blood transfusions (IUT) if fetal anemia manifests. Intravenous immunoglobulin (IVIG) or plasmapheresis may be administered to delay onset of fetal anemia and the need for IUT. The CLARITY trial aims to characterize the current SOC, clinical course, and outcomes for pregnant individuals and their offspring at high risk for EOS-HDFN.

Methods: CLARITY (NCT03755128), a prospective, multicenter, observational study enrolled individuals with singleton pregnancies at high risk for EOS-HDFN based on a prior obstetric history, high alloantibody titers, and a fetus with an incompatible blood type. The primary outcome was proportion of participants with a live birth at ≥32 weeks GA without an IUT. Other perinatal and neonatal outcome variables were evaluated up to Day 28 postpartum of the last maternal participant.

Results: Of the 15 pregnant participants, 2 (13%) achieved the primary outcome. 14/15 (93%) pregnancies resulted in a live birth, with a median GA at delivery of 36 2/7 weeks (range: 31 4/7-38 0/7). 13/15 (87%) participants required IUTs, with a median of 4 (range: 1-11) IUTs. The median GA at first IUT was 24 0/7 wks (range: 13 0/7-28 2/7). There was one case of hydrops fetalis (7%). One pregnancy resulted in fetal demise at 16 5/7 wks. 4/13 (31%) participants who received IUT experienced complications. 7/15 participants received IVIG. The 2 participants achieving the primary outcome received IVIG. 3/7 (43%) participants who received IVIG experienced IVIG-related complications. Postnatal simple transfusions were required by 8/14 (57%) neonates/infants and exchange transfusions by 4/14 (21%).

Conclusion: This study demonstrated that almost all pregnancies at high risk for EOS-HDFN managed by SOC required multiple IUTs with a high complication rate, highlighting the unmet medical need for EOS-HDFN treatments.

Presenting Author(s)

Shumyla Saeed-Khawaja, MD (she/her/hers)

Medical Director
Janssen Pharmaceutical Companies of Johnson & Johnson
Raritan, New Jersey

Senior Author(s)

DO

Dick Oepkes, MD, PhD

Professor
Department of Obstetrics, Division of Fetal Therapy, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands

Co-Author(s)

KM

Kenneth J. Moise, Jr., MD

Professor
Dell Medical School, University of Texas, Austin, TX, USA; Comprehensive Fetal Care Center at Dell Children’s Medical Center, Austin, TX, USA
Austin, Texas
EL

Enrico Lopriore, MD, PhD

Professor
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
ET

Eleonor Tiblad, MD, PhD

Senior Consultant
Center for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Stockholm, Sodermanlands Lan, Sweden
EV

EJT (Joanne) Verweij, MD, PhD

Specialist
Department of Obstetrics, Division of Fetal Therapy, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
RW

Rory Windrim, MD, PhD

Head of Department
Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
Toronto, Ontario, Canada
PP

Pranav Pandya, MD

Associate Professor
Fetal Medicine Unit, University College Hospital, Elizabeth Garrett Anderson Wing, London, UK
London, England, United Kingdom
RS

Robert M. Silver, MD

Professor
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah, USA
Salt Lake City, Utah
SE

Stephen P. Emery, MD

Director
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Pittsburgh, Pennsylvania
JS

John Smoleniec, MD, PhD

Director
Feto-Maternal Unit, Liverpool Hospital, Liverpool, Australia
Liverpool, New South Wales, Australia
OO

Olga Ocon-Hernandez, MD, PhD

Gynecologist
Fetal Medicine Unit, San Cecilio University Hospital, Granada, Spain;
Granada, Andalucia, Spain
RM

Rachel K. Morris, MBChB, PhD

Professor
Fetal Medicine Centre, Birmingham Women’s and Children’s Hospital, Birmingham, UK
Brimingham, England, United Kingdom
DH

Diane D. Harrison, MD, MPH

Project Consultant
Janssen Pharmaceutical Companies of Johnson & Johnson.
Raritan, New Jersey
VS

Valerie Smith, Mstat

Associate Director
Janssen Pharmaceutical Companies of Johnson & Johnson.
Raritan, New Jersey
LS

Lisa B. Schwartz, MD

Medical Safety Officer
Janssen Pharmaceutical Companies of Johnson & Johnson.
Raritan, New Jersey
MT

May Lee Tjoa, PhD

Global Medical Affair Leader
Janssen Pharmaceutical Companies of Johnson & Johnson.
Raritan, New Jersey
LL

Leona E. Ling, PhD

Head of Department
Janssen Pharmaceutical Companies of Johnson & Johnson
Raritan, New Jersey
YK

Yosuke Komatsu, MD, PhD

Senior Director
Janssen Pharmaceutical Companies of Johnson & Johnson.
Raritan, New Jersey