DX40
An Update on Pregnancy Outcomes Following Ocrelizumab Treatment in Patients with Multiple Sclerosis and Other Autoimmune Diseases

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Sibyl Wray, MD , Sibyl Wray MD Neurology PC, Knoxville, TN
Ludwig Kappos, MD , Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland
Sandra Vukusic, MD, PhD , Service de Neurologie et Sclerose en Plaques, Fondation EDMUS pour la Sclerose en Plaques, Hopital Neurologique Pierre Wertheimer, Lyon, France
Silvia Bader-Weder, MD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Regine Buffels, MD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Donna Masterman, MD, MS , Genentech Inc., South San Francisco, CA
Julie Napieralski, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Stephen L Hauser, MD , University of California, San Francisco, San Francisco, CA
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Background:

Ocrelizumab (OCR), a humanized monoclonal antibody that selectively targets CD20+ B cells, is approved by the U.S. Food and Drug Administration for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS), and has also been studied in clinical trials for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Objectives:

To provide an update of pregnancy outcomes in women treated with OCR during clinical trials.

Methods:

This analysis includes pregnancies in women with MS, RA and SLE in OCR clinical trials (dose range 20 to 2,000 mg) up to January 31, 2017. Across trials, women of childbearing potential were required to use two methods of contraception and continue contraception for 48 weeks after the last OCR infusion or until B cells repleted, whichever was longer. Urine pregnancy tests were performed at all infusion visits; if positive, dosing was stopped and the result confirmed with a serum pregnancy test. An embryo/fetus was considered exposed to OCR in utero if the last infusion occurred within 3 months of conception or during pregnancy or if the date of infusion was unknown. All pregnancies occurring during clinical trials were followed to determine outcome.

Results:

As previously reported, between 2008 and September 14, 2015, 46 women randomized to OCR in clinical trials (15 MS, 10 SLE, 21 RA) reported 48 pregnancies (15 MS, 11 SLE, 22 RA). This cumulative update provides approximately 16 months’ additional data on pregnancies in clinical trials up to January 31, 2017, and will review 58 pregnancies (25 MS, 11 SLE, 22 RA) reported in 56 women (25 MS, 31 non-MS [SLE or RA]). Among the 25 pregnancies in patients with MS, 14 were considered to have fetal OCR exposure, whereas 11 pregnancies had no fetal OCR exposure.

Conclusions:

As a large proportion of patients with MS are women of reproductive age, pregnancy outcomes in patients exposed to ocrelizumab are important to understand. B-cell levels in neonates following maternal exposure to ocrelizumab have not been studied in clinical trials and the effect of ocrelizumab on the immune system of the newborn is unknown. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in some infants born to mothers exposed to other anti-CD20+ antibodies during pregnancy.