• There is limited data on the use of Ocrevus in pregnant women or women who are breastfeeding.
• As of July 2023, 3,253 pregnancies had been reported in women with multiple sclerosis treated with Ocrevus.
• Available data do not suggest an increased risk of adverse pregnancy or infant outcomes with Ocrevus use.
• The ongoing SOPRANINO and MINORE studies are evaluating the placental transfer of Ocrevus from mother to baby.
• The SOPRANINO study is also evaluating the transfer of Ocrevus into breastmilk.

CIS=clinically isolated syndrome

DMT=disease modifying therapy

GA=gestational age

LLN=lower limit of normal

LMP=last menstrual period

MCA=major congenital abnormality

MS=multiple sclerosis

Ocrevus should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus.[1] There are no adequate and well-controlled data from studies in pregnant women. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy.

Please refer to the locally approved prescribing information for further information on Ocrevus.

Hellwig et al. described pregnancy outcomes of women who were exposed to Ocrevus in clinical trials in MS and post-marketing experience up to July 2023.[2] As of March 2023, more than 300,000 patients have been treated with Ocrevus globally.[3]

Maternal-exposure pregnancies in patients treated with Ocrevus

There were 3,253 maternal-exposure pregnancies in patients treated with Ocrevus for MS as of July 2023.[2] Of these pregnancies, 2,446 were prospective in nature (i.e., final outcomes were unknown at initial notification). Of the 1,145 cases with known outcomes, 957 (83.6%) resulted in live births: [2]

• 61.4% of pregnancies were full term
• 8.5% were pre-term
• 30.2% had an unknown gestational week

Details of the outcomes among prospective cases are shown in Table 1. Across exposure categories, data were in line with expected epidemiological ranges.[4,5]

Table 1. Summary of pregnancies with known outcomes [2] 

†Percentages represent fractions of the total known outcomes of the respective exposure category (not exposed in utero, exposed in utero unknown exposure, total). ‡Percentages represent fractions of the total live births for the respective exposure category (not exposed in utero, exposed in utero unknown exposure, total). The dash indicated that no cases were reported.

Major congenitial abnormalities in pregnancies with known outcomes

Fourteen major congenital abnormalities were reported among the pregnancies with known outcomes (Table 2). One live birth reported two MCAs.[2] Similar background rates of congenital abnormalities have been reported in both MS and the general population (approximately 2-4%).[4-7]

Table 2. Major congenital abnormalities [2]

†Percentages represent fractions of the total known outcomes of the respective exposure category (not exposed in utero, exposed in utero unknown exposure, total). ‡Percentages represent fractions of the total live births for the respective exposure category (not exposed in utero, exposed in utero unknown exposure, total). §The dash indicated that no cases were reported.

As of July 2023, 126 babies were potentially exposed to Ocrevus through breastfeeding.[2] Eighty (63.5%) babies also had in utero exposure. Five babies (4.0%) were vaccinated. B cell levels were available in 7 infants and the levels were within normal limits of age-specific ranges.[2]

Eleven babies experienced adverse events, primarily infections:

• Conjunctivitis and otitis media (n=1)
• Eye infection (n=1)
• Pelvic inflammation/nephritis (n=1)
• Excessive vomiting/swelling due to potential dairy allergies (n=1)
• Life-threatening breathing disorder and mild neurodermatitis (n=1)
• Vomiting and fever after 6-month vaccine (n=1)
• Upper respiratory tract infection (n=1)
• Unspecified neonatal infection (n=2)
• Respiratory syncytial virus infection (n=2)

Additional reports of Ocrevus exposure during pregnancy and lactation have been described in a number of registries, observational studies and case reports.[8-20] We refer the interested reader to the publications for more information.

Women planning pregnancies are usually excluded from clinical trials and therefore there is little evidence on the safety of DMTs during pregnancy and lactation. Available data on Ocrevus suggest no increased risk in terms of pregnancy or infant outcomes. However, there are a number of uncertainties such as whether Ocrevus crosses the placenta or is excreted in breastmilk; and if so, whether infant B cell development, immune responses or growth and development are affected. The ongoing SOPRANINO and MINORE studies are designed to address these uncertainties.[21]

SOPRANINO study (NCT04998851)

SOPRANINO is a prospective, multicenter, open-label study in women with CIS or MS, evaluating the pharmacokinetics of Ocrevus in the breast milk of lactating women and the resultant exposure and pharmacodynamic effects in the infant.[21,22] The study will enrol at least 20 women who delivered a term infant and plan to breastfeed for at least 60 days after the first postpartum Ocrevus infusion.

The co-primary endpoints of the study are 

• proportion of infants with B-cell levels below the LLN, measured 30 days after the mother’s first postpartum Ocrevus infusion, and
• estimated average daily infant dose over 60 days after the mother’s first postpartum Ocrevus infusion.

Additional endpoints will assess

• immune responses
• infant growth and development, and
• adverse events in the mother and infant.

MINORE study (NCT04998812)

MINORE is a Phase 4, prospective, multicenter, open-label study in women with CIS or MS, evaluating the placental transfer of Ocrevus, and the corresponding pharmacodynamic effects in infants.[21,23] The study will enrol approximately 44 women between GWk 22–26, whose last Ocrevus dose occurred at any time from 6 months before the LMP until the end of the first trimester. 

The primary endpoint of the study is the proportion of infants with B-cell levels below LLN at Week 6 of life. Key secondary endpoints are

• serum Ocrevus levels in umbilical cord blood, and
• infant humoral immune responses to vaccinations.

1. Roche Internal Regulatory Report (Accessed on 8 August 2023).
2. Hellwig K, Oreja-Guevara C, Vukusic C, et al. Pregnancy and Infant Outcomes in Women Receiving Ocrelizumab for the Treatment of Multiple Sclerosis: Analysis of the Largest Available Outcomes Database. Presented at the 9th Joint European Committee for Treatment and Research in MS - Americas Committee for Treatment and Research in MS Meeting in Milan, Italy; October 11-13, 2023. ECTRIMS-ACTRIMS Poster #P061.
3. Roche Internal Safety Report (Accessed on 18th October 2023).
4. Lopez-Leon S, Geissbühler Y, Sabidó M, et al. A systematic review and meta-analyses of pregnancy and fetal outcomes in women with multiple sclerosis: a contribution from the IMI2 ConcePTION project. J Neurol 2020;267:2721-2731. https://www.ncbi.nlm.nih.gov/pubmed/32444984
5. Centers for disease control and prevention (CDC). Update on overall prevalence of major birth defects - Atlanta, Georgia, 1978-2005. January 11, 2008. Available at https://www.ncbi.nlm.nih.gov/pubmed/18185492.
6. Andersen J, Sellebjerg F, Magyari M. Pregnancy outcomes after early fetal exposure to injectable first-line treatments, dimethyl fumarate, or natalizumab in Danish women with multiple sclerosis. Eur J Neurol 2023;30:162-171. https://www.ncbi.nlm.nih.gov/pubmed/36098960
7. MacDonald S, McElrath T, Hernández-Díaz S. Pregnancy Outcomes in Women With Multiple Sclerosis. Am J Epidemiol 2019;188:57-66. https://www.ncbi.nlm.nih.gov/pubmed/30165561
8. Thiel S, Ciplea A, Gold R, et al. The German Multiple Sclerosis and Pregnancy Registry: rationale, objective, design, and first results. Ther Adv Neurol Disord 2021;14:17562864211054956. https://www.ncbi.nlm.nih.gov/pubmed/34840606
9. Schwake C, Steinle J, Thiel S, et al. Effects of anti-CD20 therapies on infant health and physiological B-cell development if administered before or during pregnancy and/or lactation. Mult. Scler. 2022;28(3_suppl):29-30. https://journals.sagepub.com/toc/msja/28/3_suppl
10. Kumpfel T, Thiel S, Meinl I, et al. Anti-CD20 therapies and pregnancy in neuroimmunologic disorders: A cohort study from Germany. Neurol Neuroimmunol Neuroinflamm 2001;8:https://pubmed.ncbi.nlm.nih.gov/33334856
11. Yeh W, VanderWalt A, Kermode A, et al. Disease activity during pregnancy and postpartum in women with MS receiving ocrelizumab in a real-world cohort. Presented at the Congress of the European Academy of Neurology in Vienna, Austria; June 25-28, 2022. EAN Oral presentation. https://www.ean.org/congress2022
12. Sadovnick D, Criscuoli M, Yee I, et al. The road to conception for women with multiple sclerosis. Mult Scler J Exp Transl Clin None;7:20552173211032313. https://www.ncbi.nlm.nih.gov/pubmed/34350028
13. Alroughani R, Jasem A, AlMojel M, et al. Safety and Efficacy of Ocrelizumab in Multiple Sclerosis - a Real Clinical Sitting in Kuwait. Presented at the Americas Committee for Treatment and Research in Multiple Sclerosis Forum in San Diego, CA; February 23-25, 2023. ACTRIMS Abstract #P171. https://forum.actrims.org/
14. Luciani K, Katz J, Lathi E, et al. ACAPELLA: real world experience with ocrelizumab: an observational study evaluating safety in patients with relapsing and progressive multiple sclerosis. Presented at the Consortium of Multiple Sclerosis Centers Annual Meeting in Nashville, TN, Nashville; May 30 - June 2, 2018. CMSC Poster.
15. Gitman V, Stavropoulos A, Saenz V, et al. Pregnancy outcomes of women with multiple sclerosis treated with ocrelizumab in Canada: A descriptive analysis of real-world data. Mult Scler Relat Disord 2022;62:103792. https://www.ncbi.nlm.nih.gov/pubmed/35452964
16. Zhovtis_Ryerson L, Gragui D, Chinea F, et al. Ocrelizumab Use and Family Planning: New York University Multiple Sclerosis Center Experience. Presented at the Consortium of Multiple Sclerosis Centers Annual Meeting in Aurora, Colorado; May 31 - June 3, 2023. CMSC Abstract #DMT43. https://cmscscholar.org/2023-annual-meeting/
17. Chey S, Kermode A. Pregnancy outcome following exposure to ocrelizumab in multiple sclerosis. Mult Scler J Exp Transl Clin None;8:20552173221085737. https://www.ncbi.nlm.nih.gov/pubmed/35284087
18. Rolfes M, Rutatangwa A, Waubant E, et al. Ocrelizumab exposure in the second trimester of pregnancy without neonatal B-cell depletion. Mult Scler Relat Disord. E-pub Date: July 2020. DOI # 10.1016/j.msard.2020.102398. https://www.ncbi.nlm.nih.gov/pubmed/32707531
19. Anderson A, Poole S, Rowles W, et al. Anti-CD20 monoclonal antibody therapy after 59 pregnancies in women with neurological conditions: Low breastmilk transfer and normal infant development in a multicenter cohort. Presented at the European Committee for Treatment and Research in Multiple Sclerosis in Amsterdam, The Netherlands; October 26-28, 2022. ECTRIMS Oral presentation #O037. https://2022.ectrims-congress.eu/
20. Ciplea AI, Langer-Gould A, de VA, et al. Monoclonal antibody treatment during pregnancy and/or lactation in women with MS or neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. E-pub Date: July 2020. DOI # 10.1212/NXI.0000000000000723. https://www.ncbi.nlm.nih.gov/pubmed/32327455
21. Bove R, Hellwig K, Pasquarelli N, et al. Ocrelizumab during pregnancy and lactation: Rationale and design of the MINORE and SOPRANINO studies in women with MS and their infants. Mult Scler Relat Disord 2022;64:103963. https://www.ncbi.nlm.nih.gov/pubmed/35753176
22. Bove R, Pasquarelli N, Borriello F, et al. B-cell levels and immunity in breastfed infants of women with MS treated with ocrelizumab: design of a Phase 4 study (SOPRANINO). Presented at the European Committee for Treatment and Research in Multiple Sclerosis in virtual; October 13-15, 2021. ECTRIMS Poster #P686. https://www.ectrims-congress.eu/2021.html
23. Hellwig K, Pasquarelli N, Borriello F, et al. Rationale and design of a Phase 4 study exploring B-cell levels and immune responses in infants born to women with MS who were exposed to ocrelizumab up to 6 months before or during the first trimester of pregnancy (the MINORE study). Presented at the European Committee for Treatment and Research in Multiple Sclerosis in virtual; October 13-15, 2021. ECTRIMS Poster. https://www.ectrims-congress.eu/2021.html