Treatment Strategies and Disease Activity During Pregnancy and Postpartum Real-World Data From the Swiss Multiple Sclerosis Cohort

Backgrounds and Objectives Managing multiple sclerosis (MS) during pregnancy and postpartum is a therapeutic challenge. We aim to describe therapy regimens, clinical and MRI disease activity, and serum neurofilament light chain (sNfL) levels in all pregnancies observed between 2012 and 2023 among participants of the Swiss MS cohort. Methods We assessed the treatment strategies during pregnancy and 1 year postpartum in all included pregnancies. We compared pregnancies continuously exposed to high-efficacy disease-modifying therapies (cHET: anti-CD20 monoclonal antibodies (aCD20) and natalizumab [NTZ]) with those where other therapeutic regimens (OTRs) were used. Disease activity was assessed by occurrence of relapses or new or enlarging T2w lesions (neT2Ls), as well as sNfL Z scores. We estimated odds ratios adjusted for age, disease duration, Expanded Disability Status Scale (EDSS) score, and previous relapse rate using generalized estimating equation (GEE) models for the relapse endpoint and using Firth logistic regression for MRI activity. sNfL Z scores were compared between treatment categories at sampling using GEE models. Results We analyzed 123 pregnancies in 93 women (median age [interquartile range {IQR}] 32.2 years [29.3, 35.7]; EDSS score [IQR] 1.5 [1.0, 2.0]). The last disease-modifying therapy (DMT) before birth was NTZ in 29 (23.5%) and aCD20 in 25 (20.3%) pregnancies; of those, 3 and 24 were exposed until birth, respectively (cHET). Fingolimod was the last treatment before birth in 25 pregnancies (20.3%), stopped in all before or after confirmation of pregnancy. Other DMTs were used in 39 pregnancies (31.7%); 5 remained untreated. Compared with cHET, patients with pregnancies under OTRs had higher proportions of relapses (34.4% vs 13.0%; n = 113, OR 4.52, 95% CI [1.35–15.11], p = 0.0142) and neT2Ls (40.9% vs 3.8%; n = 91, OR 9.15, 95% CI [2.14–85.21], p = 0.0013). sNfL Z scores during pregnancy and postpartum were higher in patients untreated at sampling compared with patients under high-efficacy DMT (HET) (+0.43 Z score units, 95% CI [0.05–0.81], p = 0.0255). No serious adverse events were observed. Discussion Treatment strategies for pregnant patients with MS were heterogeneous, and continuous exposure to HET showed superior efficacy against acute disease activity compared with other DMTs or no treatment. Further studies are needed to confirm these results and assess maternal and fetal longer term outcomes.