番茄社区

Women with multiple sclerosis (MS) who were treated with ocrelizumab (Ocrevus) had no increased risk of adverse pregnancy and infant outcomes, prospective data showed.

Cumulative data did not suggest an increased risk of preterm birth, major congenital anomalies, or other adverse outcomes with ocrelizumab in utero exposure and were consistent with epidemiological data, reported Celia Oreja-Guevara, MD, of Hospital Clínico San Carlos in Madrid, Spain.

The findings represent the largest dataset of pregnancy outcomes for an anti-CD20 therapy, Oreja-Guevara said in a presentation at the 2022 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

This may be reassuring news to patients, as most people who develop MS are women of childbearing age.

"Family planning poses special challenges for MS treatment planning since most disease-modifying therapies are recommended or even required to be discontinued during pregnancy planning, throughout pregnancy, and during breastfeeding," said co-author Riley Bove, MD, of University of California San Francisco.

"Ocrelizumab is used by hundreds of thousands of MS patients, many of whom aim for a pregnancy," she told 番茄社区. "These data provide much needed evidence to help inform decision-making for women and their doctors on how to effectively manage this chronic, progressive condition."

Globally, more than 250,000 people with MS have started ocrelizumab treatment as of March 2022, and the number of women with MS exposed to ocrelizumab before, during, and after pregnancy is increasing, Oreja-Guevara said.

The investigators had very limited information on infant outcomes through the first year of life.

Two prospective phase IV studies may shed light on infant outcomes, Bove noted. The ongoing study is assessing infant B-cell levels and ocrelizumab pharmacokinetics across the placenta, while is studying B-cell levels in infants of lactating women on ocrelizumab.

The present study was based on information in the Roche Global Safety Database and included clinical study data, spontaneous reports, published literature, and findings from non-interventional programs. Reports were from November 2008 through March 2022.

Oreja-Guevara and colleagues defined in utero fetal exposure as the mother receiving one or more ocrelizumab infusions within 3 months before her last menstrual period or during pregnancy.

Fetal death was termed spontaneous abortion at 22 or fewer gestational weeks, or stillbirth if later. Preterm births were live births with fewer than 37 gestational weeks completed. Major congenital anomalies were classified based on European Surveillance of Congenital Anomalies (EUROCAT) Guide 1.4.

As of March 2022, 2,020 pregnancies had been reported among women treated with ocrelizumab. Median age at last menstrual period was 32. The timing of last dose with respect to last menstrual period was known for 56% of prospective cases.

Outcomes were known for 286 exposed pregnancies and 163 unexposed pregnancies.

Among 286 pregnancies exposed to ocrelizumab, 78.7% resulted in live births and 9.3% of births were pre-term. Ectopic pregnancy occurred in 1.4%, elective termination occurred in 11.5%, and spontaneous abortion occurred in 8.0%. In total, 0.3% of exposed pregnancies resulted in stillbirth.

Among 163 unexposed pregnancies, 74.1% resulted in live births (10.1% preterm), 2.7% were ectopic, 4.8% had elective termination, and 18.4% had spontaneous abortion. No stillbirths were reported.

Among both prospective and retrospective cases in the database, 1.1% of ocrelizumab-exposed births were full-term with a major congenital anomaly, and 1.1% were preterm with a major congenital anomaly. No fetal deaths with major congenital anomalies occurred.

For comparison, around 2 to 3% of children born in Europe every year will have a major congenital anomaly, Oreja-Guevara noted.

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