Placental and Breastmilk Transfer of Ocrelizumab from Women with Multiple Sclerosis to Infants and the Potential Impact on B-Cell Levels: Primary Analysis of the Prospective, Multicenter, Open-label, Phase IV Studies MINORE and SOPRANINO
Riley Bove1, Celia Oreja-Guevara2, Sandra Vukusic3, Anna Shah4, Edith Graham5, Thomas McElrath6, Carlo Pietrasanta7, Ruth Dobson8, Elisabeth Maillart9, Dina Jacobs10, Heidemarie Kletzl11, Agne Kazlauskaite11, Dusanka Zecevic11, Catarina Raposo11, Licinio Craveiro11, Chien-Ju Lin12, Noemi Pasquarelli11, Kerstin Hellwig13
1Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA, 2Neurology, Hospital Clínico San Carlos, IdISSC, Madrid, Spain, 3Service de Neurologie et Sclérose en Plaques, Fondation Eugène Devic EDMUS contre la Sclérose en Plaques, Hôpital Neurologique Pierre Wertheimer, Lyon, France, 4Department of Neurology, Rocky Mountain MS Center, University of Colorado School of Medicine, CO, USA, 5Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, IL, USA, 6Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 7Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy, 8Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK, 9Neurology Department Hôpital de la Pitié Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France, 10Department of Neurology, Perelman School of Medicine at the Hospital of the University of Pennsylvania, Philadelphia, PA, USA, 11F. Hoffmann-La Roche Ltd, Basel, Switzerland, 12Roche Products Ltd, Welwyn Garden City, UK, 13Katholisches Klinikum Bochum, St. Josef Hospital, Universitätsklinikum, Bochum, Germany
Objective:

To measure placental and breastmilk transfer of ocrelizumab (OCR) in women with MS and evaluate the impact on B-cell levels in infants potentially exposed during pregnancy (MINORE [NCT04998812]) or breastfeeding (SOPRANINO [NCT04998851]).

Background:

Traditional MS pregnancy and breastfeeding management prioritizes infant safety, with the mother at risk of increased disease activity upon disease-modifying therapy discontinuation; however, prospective data to establish safety for mother and baby are lacking.

Design/Methods:

In MINORE, 35 pregnant women with MS whose last OCR infusion occurred ≤6 months prior to the last menstrual period/during the first trimester were enrolled. Primary endpoint was the proportion of infants with B-cell levels below the lower limit of normal (LLN) at W6 of life. In SOPRANINO, 13 breastfeeding women receiving OCR and their infants were enrolled (W2–24 at infusion). Co-primary endpoints: proportion of infants with B-cell levels <LLN 30 days post-infusion and OCR average daily infant dose (ADID) over 60 days post-infusion. Key secondary endpoints: concentration of OCR in the infant’s umbilical cord blood serum, W6 (MINORE) and 30 days post-infusion (SOPRANINO).

Results:

MINORE: OCR was undetectable in most infants, both at birth in the umbilical cord blood (33/35, 94.3%) and at W6 in the serum (32/33, 97.0%); where detectable, OCR levels were close to the limit of quantification and below therapeutic levels. SOPRANINO: OCR levels in breastmilk were negligible (mean ADID: 64.5 µg) and undetectable in infant serum at 30 days post-infusion (9/9, 100%). All infant B-cell levels were above the age-specific LLN in MINORE (W6: 34/34, 100%) and SOPRANINO (30 days post-infusion: 10/10, 100%). Adverse events were typical for delivery, postpartum and infancy and in line with the established OCR safety profile.

Conclusions:

The results indicate that breastfeeding and pregnancy planning are compatible with ocrelizumab treatment and can support clinicians caring for women with MS in making evidence-based treatment decisions.

10.1212/WNL.0000000000211193
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