Disease Activity During Pregnancy and Postpartum in Women With Multiple Sclerosis Treated With Ocrelizumab or Rituximab Before Pregnancy.

Abstract

Background and objectives: Preliminary data suggest sustained disease control with ocrelizumab (OCR) or rituximab (RTX) in women with multiple sclerosis (MS) after pregnancy suspension; however, the influence of washout duration and cumulative dosing remains unknown. This study investigates disease activity during and after pregnancy in women with relapsing-remitting MS treated with OCR/RTX before pregnancy.

Methods: In this cohort study, pregnancies of women treated with OCR/RTX documented in the German MS and Pregnancy Registry were stratified by timing of last infusion (≥ or <4 months to last menstrual period [LMP]) and number of cycles (≥ or <2 cycles). Relapses treated with high-dose glucocorticosteroids were analyzed, as was persistent disability (following a relapse) at 1-year postpartum, defined as a ≥2.0-point increase in Expanded Disability Status Scale (EDSS) or new/worsening ambulatory impairment (Severe Relapse Disability Composite Score [SRDCS]).

Results: Of 294 pregnancies among 275 women, only 28.6% (n = 84) suspended OCR/RTX ≥4 months before LMP and most (79.3% [n = 233]) received ≥2 cycles. Relapses during pregnancy (2.0%) and within 12 months postpartum (8.5%) were rare. Four women (1.6%) reached the SRDCS postpartum. Neither the time of last infusion nor the number of cycles was associated with a higher relapse risk during pregnancy (time between OCR/RTX and LMP: <4 months adjusted OR: 0.60, CI: 0.09-5.02, p value: 0.60; number of cycles: <2 cycles adjusted OR: 2.23, CI: 0.34-15.5, p value: 0.39) or postpartum (time between OCR/RTX and LMP: <4 months adjusted OR: 0.62, CI: 0.23-1.77, p value: 0.36; number of cycles: <2 cycles adjusted OR: 0.64, CI: 0.16-2.03, p value: 0.48, time of anti-CD20 antibody restart postpartum: >6 weeks adjusted OR: 1.15, CI: 0.37-4.11, p value: 0.82) or with reaching the SRDCS or EDSS worsening postpartum. In women receiving ≥2 cycles and interrupting treatment <4 months before LMP, numerically fewer relapses during pregnancy could be observed (1/163: 0.6% vs 5/131: 3.8%, p value: 0.09).

Discussion: Relapses and disability during and after pregnancy after OCR/RTX interruption are rare and independent of timing and number of cycles. However, potential differences may not be detectable due to the low number of events and should be evaluated in larger studies. In addition, the applicability to ofatumumab, given its different dosing interval, remains unclear.