Abstract
Recent studies estimated an incidence of 4–25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013–2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11–3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses.
Highlights
Multiple sclerosis (MS) affects 2.8 million people worldwide [1] and is considered the most prevalent cause of disability in young adults, resulting in physical, cognitive and psychosocial impairments [2]
We identified a total of 27 women (3% of all patients treated with FTY in the whole cohort) who stopped FTY treatment for planned or unplanned pregnancy
11% switched from natalizumab due to a high risk of progressive multifocal leukoencephalopathy, and 15% were naïve to disease-modifying drugs (DMDs) with an aggressive disease course
Summary
Multiple sclerosis (MS) affects 2.8 million people worldwide [1] and is considered the most prevalent cause of disability in young adults, resulting in physical, cognitive and psychosocial impairments [2]. MS is Extended author information available on the last page of the article most prevalent in women of reproductive age [5, 6]; pregnancy issues associated with new treatments are highly relevant. Previous studies on the course of MS during pregnancy were performed in patients either not exposed or minimally exposed to DMDs before pregnancy [9] This situation does not accurately reflect current clinical practice, in which greater than 80% of patients with early-stage RRMS receive DMDs [10]. Many DMDs and symptomatic treatments used in MS are not considered completely safe in women who are attempting to conceive, are pregnant or are breastfeeding [12,13,14]. In MS, withdrawal of certain DMDs, mainly lymphocyte antitrafficking therapies, such
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