Pregnancy Outcomes in Alemtuzumab-Treated Patients With RRMS

Abstract

Here we provide updated pregnancy outcomes in alemtuzumab-treated female patients in phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies. Patients received annual treatment courses of alemtuzumab and could enter an extension study (NCT00930553), with as-needed alemtuzumab retreatment (≥1 year apart). Pregnant/lactating patients were treatment-ineligible but remained on study for safety follow-up. As of July 1, 2015, 193 pregnancies occurred in 136 of 972 alemtuzumab-treated female patients; 167 were completed, 16 were ongoing, and 10 had unknown outcomes. Of completed pregnancies, 110 (66%) were live births with no congenital abnormalities or birth defects among 94 patients (at conception: mean age, 31.5 years; mean EDSS, 1.7; mean time since initial MS relapse, 6.6 years; mean time since last MS relapse, 3.5 years; mean time from previous alemtuzumab infusion, 27.9 months). There were 37 (22%) spontaneous abortions, 19 (11%) elective abortions, and 1 (0.6%) previously reported stillbirth. In alemtuzumab MS clinical studies, the most common pregnancy outcome was full-term live birth, with no evidence of teratogenicity to date. The rate of spontaneous abortion with alemtuzumab was comparable with rates observed in other MS patients and general populations. Ongoing surveillance is needed.Study supported by Sanofi Genzyme and Bayer Healthcare Pharmaceuticals.

Pharmacotherapeutic considerations in women with multiple sclerosis

“…A total of 167 completed pregnancies with a mean time from previous ALZ infusion to conception of 27.9 months resulted in 66% live births with no congenital malformations or birth defects, 22% spontaneous abortions, 11% elective abortions and one stillbirth. The rate of spontaneous abortion among ALZ exposed pregnancies was reported to be similar to that of other MS patients and the general population [96]. A case series consisting of 59 pregnancies to 58 women from Germany, Norway and Serbia included 18 pregnancies exposed to ALZ (last ALZ infusion <4 months before last menstrual period) and 41 unexposed pregnancies with conception > 4 months after last ALZ infusion.…”

The use of alemtuzumab in patients with relapsing-remitting multiple sclerosis: the Gulf perspective

“…There were 22% spontaneous abortions and 1% stillbirths. 67 Further studies on the safety and potential risks of alemtuzumab in pregnancy are also recommended. 66 …”

Pregnancy post autologous stem cell transplant with BEAM conditioning for multiple sclerosis

“…When compared, alemtuzumab-treated female patients in the phase 2 CAMMS223 and phase 3 CARE-MS I and MS II trials, the rate of pregnancy in the alemtuzumab-treated registry group was significantly higher than our post-AHSCT cohort, with approximately 193 pregnancies having occurred in 136 of 972 treated female patients. 8 While natalizumab use appears safe in early pregnancy, there remains sparse literature on exact fertility rates, largely because natalizumab is often withheld or dose-reduced during pregnancy because of an association of 33% with haematological abnormalities in newborns in women receiving natalizumab in their third trimester. 9 Similarly, while post-marketing registries up to 2019 appear to show no increased risk of adverse pregnancy outcomes for ocrelizumab, limited literature exists and data continues to be collected and assessed.…”