Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions

Annika Anderson¹, William Rowles¹, Shane Poole¹, Ayushi Balan¹, Carolyn Bevan², Rachel Brandstadter³, Andrea I Ciplea⁴, Joanna Cooper⁵, Michelle Fabian⁶, Thomas W Hale⁷, Dina Jacobs³, Mihir Kakara³, Kristen M Krysko^{8

9}, Erin E Longbrake¹⁰, Jacqueline Marcus¹¹, Pavle Repovic¹², Claire S Riley¹³, Andrew R Romeo¹⁴, Alice Rutatangwa¹, Timothy West¹⁵, Kerstin Hellwig⁴, Sara C LaHue^{1

16}, Riley Bove¹

Affiliations

¹ UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
² Department of Neurology, Northwestern University, Chicago, Illinois, USA.
³ Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Neurology, Ruhr University Bochum, Bochum, Germany.
⁵ Sutter East Bay Medical Group, Lafayette, California, USA.
⁶ Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁷ Texas Tech University Health Sciences Center, Amarillo, Texas, USA.
⁸ Division of Neurology, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
⁹ Li Ka Shing Knowledge Institute, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Neurology, Yale University, New Haven, Connecticut, USA.
¹¹ Department of Neurology, Kaiser Permanente San Francisco, San Francisco, California, USA.
¹² Department of Neurology, Swedish Medical Center, Seattle, Washington, USA.
¹³ Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
¹⁴ Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ Rocky Mountain MS Center, Salt Lake City, Utah, USA.
¹⁶ Buck Institute for Research on Aging, Novato, California, USA.

PMID: 37675826
PMCID: PMC10647007
DOI: 10.1002/acn3.51893

Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions

Annika Anderson et al. Ann Clin Transl Neurol. 2023 Nov.

. 2023 Nov;10(11):2053-2064.

doi: 10.1002/acn3.51893. Epub 2023 Sep 7.

Authors

Affiliations

¹ UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
² Department of Neurology, Northwestern University, Chicago, Illinois, USA.
³ Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Neurology, Ruhr University Bochum, Bochum, Germany.
⁵ Sutter East Bay Medical Group, Lafayette, California, USA.
⁶ Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁷ Texas Tech University Health Sciences Center, Amarillo, Texas, USA.
⁸ Division of Neurology, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
⁹ Li Ka Shing Knowledge Institute, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Neurology, Yale University, New Haven, Connecticut, USA.
¹¹ Department of Neurology, Kaiser Permanente San Francisco, San Francisco, California, USA.
¹² Department of Neurology, Swedish Medical Center, Seattle, Washington, USA.
¹³ Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
¹⁴ Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ Rocky Mountain MS Center, Salt Lake City, Utah, USA.
¹⁶ Buck Institute for Research on Aging, Novato, California, USA.

PMID: 37675826
PMCID: PMC10647007
DOI: 10.1002/acn3.51893

Abstract

Objective: Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes.

Methods: Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes.

Results: The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05-0.4; RTX: 0.03 μg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse.

Interpretation: These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.

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Conflict of interest statement

All authors’ financial disclosures are included in the attached ICMJE forms. The drugs, ocrelizumab and rituximab, are tested in this study. Genentech (a subsidiary of the Roche Group) is the manufacturer of ocrelizumab and co‐markets rituximab, a drug developed and co‐marketed by Biogen. Potential conflict of interest disclosures related to the study are outlined below: CB has received scientific advisory board fees and travel support from Genentech which manufactures and co‐markets the AIC reports speaker honoraria from Biogen which co‐markets a drug tested in this study. DJ has received research support and consulting/scientific advisory board fees from Biogen and Genentech which manufacture and co‐market drugs tested in this study. KMK is an advisory board member for Roche and has received grants from Roche which manufactures and co‐markets a drug tested in this study. KMK also reports support from an MS fellowship grant during her fellowship from Biogen, which co‐markets a drug tested in this study. EEL reports research support and consulting/advisory board fees from Genentech which manufactures and co‐markets the drugs tested in this study. PR reports consulting and/or speaking honoraria from Genentech which manufactures and co‐markets the drugs tested in this study. CSR reports consulting fees or honoraria from Genentech which manufactures and co‐markets the drugs tested in this study. TW has received honoraria for speaking and education activities through Biogen Idec which co‐markets a drug tested in this study. KH has received research support, consulting, speaking, and/or advisory board fees from Roche and Biogen which manufacture and co‐market the drugs tested in this study. RB reports research support from Biogen and Roche‐Genentech which manufactures and co‐markets the drugs tested in this study.

Figures

**Figure 1**
Timing of maternal relapse and DMT use relative to pregnancy in women with MS (n = 57 pregnancies). Each line on the y‐axis indicates a single pregnancy. The x‐axis indicates observation period from 12 months before conception, through pregnancy, and up to 12 months postpartum. The color of each line indicates maternal DMT at a given timepoint; anti‐CD20 and natalizumab treatment were graphed with extension to 6M and 1M past the last infusion, respectively. Conception is indicated by a circle. Relapse is indicated by a triangle and was assessed from 12 months before conception to 12 months after delivery.

**Figure 2**
Anti‐CD20 mAb in breastmilk (n = 32 Ocrelizumab and n = 21 Rituximab treatment cycles). Breastmilk concentration (μg/mL) in 51 pregnancies up to 174 days post‐infusion. Lines connect samples from a given individual during a single collection period. Pre‐infusion concentration was assumed to be 0 μg/mL. Samples below the detection threshold (ocrelizumab: 0.16 μg/mL, rituximab: 0.01 μg/mL) were plotted arbitrarily at concentrations under the threshold for visual clarity. Pregnancies with no detectable concentration of anti‐CD20 mAb in any sample are plotted in black.

**Figure 3**
Infant CD19 levels (n = 9 infants). Individual lines connect collection timepoints provided by a given infant. Red timepoints indicate sample collection in infant wih maternal treatment with mAb <6 months before conception (n = 8). Blue timepoints indicate sample collection after infant exposure to mAb via lactation (n = 4, breastfeeding after maternal postpartum infusion). Boundaries indicating the 10th–90th percentiles for absolute CD19+ cells among healthy infants (300–2000 CD19+ cells/μL aged 0–3 months, 430–3000 CD19+ cells/μL 3–6 months) are plotted as a gray dashed line.

**Figure 4**
Infant growth velocity. Weight, length, and head circumference from birth to 12 months (n = 56). Normal percentiles, defined by the WHO as 3rd‐97th percentiles, are graphed in red. Each black line corresponds to a given infant relative to age indicated on the x‐axis. There were no statistical differences in growth between breastfed and non‐breastfed infants (weight, height, and head circumference: p > 0.05 on Fisher's exact test).

**Figure 5**
Infant development ASQ scores in five domains of development (n = 54 infants). “Above cutoff” and “monitoring range” indicated on schedule development. Lines connect timepoints for a given infant. Surveys were not adjusted for gestational age at delivery. There were no statistical differences in growth between breastfed and non‐breastfed infants (p > 0.05 for each domain on Fisher's exact test).

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Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions

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Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions

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