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July 2020; 7 (4) ArticleOpen Access

Rituximab, MS, and pregnancy

Jessica B. Smith, Kerstin Hellwig, Katharina Fink, Deirdre J. Lyell, Fredrik Piehl, Annette Langer-Gould
First published May 1, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000734
Jessica B. Smith
From the Department of Research & Evaluation (J.B.S.), Kaiser Permanente Southern California; Department of Neurology (K.H.), St. Josef Hospital, Bochum, Germany; Department of Clinical Neuroscience (K.F., F.P.), Karolinska Institute; Center for Neurology (K.F.), Academic Specialist Center, Stockholm, Sweden; Department of Obstetrics & Gynecology – Maternal Fetal Medicine (D.J.L.), Stanford University School of Medicine, Stanford, CA; Department of Neurology (F.P.), Karolinska University Hospital, Stockholm, Sweden; and Department of Neurology (A.L.-G.), Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles, CA.
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Kerstin Hellwig
From the Department of Research & Evaluation (J.B.S.), Kaiser Permanente Southern California; Department of Neurology (K.H.), St. Josef Hospital, Bochum, Germany; Department of Clinical Neuroscience (K.F., F.P.), Karolinska Institute; Center for Neurology (K.F.), Academic Specialist Center, Stockholm, Sweden; Department of Obstetrics & Gynecology – Maternal Fetal Medicine (D.J.L.), Stanford University School of Medicine, Stanford, CA; Department of Neurology (F.P.), Karolinska University Hospital, Stockholm, Sweden; and Department of Neurology (A.L.-G.), Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles, CA.
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Katharina Fink
From the Department of Research & Evaluation (J.B.S.), Kaiser Permanente Southern California; Department of Neurology (K.H.), St. Josef Hospital, Bochum, Germany; Department of Clinical Neuroscience (K.F., F.P.), Karolinska Institute; Center for Neurology (K.F.), Academic Specialist Center, Stockholm, Sweden; Department of Obstetrics & Gynecology – Maternal Fetal Medicine (D.J.L.), Stanford University School of Medicine, Stanford, CA; Department of Neurology (F.P.), Karolinska University Hospital, Stockholm, Sweden; and Department of Neurology (A.L.-G.), Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles, CA.
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Deirdre J. Lyell
From the Department of Research & Evaluation (J.B.S.), Kaiser Permanente Southern California; Department of Neurology (K.H.), St. Josef Hospital, Bochum, Germany; Department of Clinical Neuroscience (K.F., F.P.), Karolinska Institute; Center for Neurology (K.F.), Academic Specialist Center, Stockholm, Sweden; Department of Obstetrics & Gynecology – Maternal Fetal Medicine (D.J.L.), Stanford University School of Medicine, Stanford, CA; Department of Neurology (F.P.), Karolinska University Hospital, Stockholm, Sweden; and Department of Neurology (A.L.-G.), Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles, CA.
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Fredrik Piehl
From the Department of Research & Evaluation (J.B.S.), Kaiser Permanente Southern California; Department of Neurology (K.H.), St. Josef Hospital, Bochum, Germany; Department of Clinical Neuroscience (K.F., F.P.), Karolinska Institute; Center for Neurology (K.F.), Academic Specialist Center, Stockholm, Sweden; Department of Obstetrics & Gynecology – Maternal Fetal Medicine (D.J.L.), Stanford University School of Medicine, Stanford, CA; Department of Neurology (F.P.), Karolinska University Hospital, Stockholm, Sweden; and Department of Neurology (A.L.-G.), Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles, CA.
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Annette Langer-Gould
From the Department of Research & Evaluation (J.B.S.), Kaiser Permanente Southern California; Department of Neurology (K.H.), St. Josef Hospital, Bochum, Germany; Department of Clinical Neuroscience (K.F., F.P.), Karolinska Institute; Center for Neurology (K.F.), Academic Specialist Center, Stockholm, Sweden; Department of Obstetrics & Gynecology – Maternal Fetal Medicine (D.J.L.), Stanford University School of Medicine, Stanford, CA; Department of Neurology (F.P.), Karolinska University Hospital, Stockholm, Sweden; and Department of Neurology (A.L.-G.), Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles, CA.
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Citation
Rituximab, MS, and pregnancy
Jessica B. Smith, Kerstin Hellwig, Katharina Fink, Deirdre J. Lyell, Fredrik Piehl, Annette Langer-Gould
Neurol Neuroimmunol Neuroinflamm Jul 2020, 7 (4) e734; DOI: 10.1212/NXI.0000000000000734

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    Figure 1 Pregnancy outcomes after RTX exposure in women with MS

    Depicted are the pregnancy outcomes of women with MS who were exposed to at least 1 dose of RTX before known pregnancy. Fifteen women had 23 first-trimester miscarriages. No miscarriages occurred during the second trimester. One preterm birth at 36w, followed a normal pregnancy with NSVD. Two pregnancies ended with PROMs, resulting in delivery of 3 preterm infants, all of whom were low birthweight but were not small for gestational age. The twins were of very low birthweight. One twin died from an intraventricular hemorrhage 6 days after birth. Among the full-term infants, 1 born by vacuum-assisted vaginal delivery had a stroke and seizures. There were no cases of chorioamnionitis and no adverse pregnancy outcomes due to systemic maternal infections. g = grams; NSVD = normal spontaneous vaginal delivery; PROM = premature rupture of membrane; RTX = rituximab, 1st = first, gestational age is indicated by weeks (w).

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    Figure 2 Periconceptual and postpartum RTX infusions and MS relapses after the initiation of RTX among pregnancies ending in live births

    Depicted are the number of RTX infusions (blue bars) and MS relapses (orange line) that occurred during the study period among pregnancies ending in live births (n = 37) who received at least 1 RTX infusion before conception or during the first trimester (Tri). The study period encompasses the 12 months before conception, pregnancy, and the 12 months postpartum divided into 3-month intervals. Four women relapsed during the study period after initiating RTX. Only 2 women relapsed during pregnancy or the postpartum period, 1 during the 2nd trimester of pregnancy who received her most recent RTX infusion 3 months before conception (R1), and one between 6 and 9 months postpartum who received her most recent RTX infusion 3.9 months before conception (R2). Two additional women had relapses after RTX initiation in the 12 months before conception; 1 woman 10.3 months before conception who received her most recent RTX infusion 4.5 months before relapse, and another woman who relapsed 8.5 months before conception, 0.9 months after her first RTX infusion. Most pregnancies (n = 25, 68%) occurred within 6 months of their most recent RTX infusion. Increasing numbers of RTX infusions over the study period are denoted by increasingly lighter shades of blue. The darkest blue shading indicates the first RTX infusion during the study period of which most (n = 32) occurred during the 12 months before conception. The woman who is depicted with her first RTX infusion occurring 0–3 months postpartum had her last RTX infusion more than 12 months before conception. Two additional women received their last RTX infusion >12 months before conception; neither had resumed RTX before the end of the study period. Twenty-one women received their first ever infusion of RTX in the year before pregnancy and 2 shortly after their last menstrual period. Twelve women received 2 infusions, 6 received 3 infusions, 4 had 4 infusions, and 3 had 5 RTX infusions (lightest shade of blue) during the study period. The number of women at risk are those who had received at least 1 infusion of RTX before pregnancy (or shortly after conception). In the postpartum period, the number of women at risk also incorporates the duration of the follow-up. No women have been lost to follow-up, but 11 women are less than 12 months postpartum. RTX = rituximab.

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