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Multicenter Study
. 2024 May;31(5):e16228.
doi: 10.1111/ene.16228. Epub 2024 Feb 20.

Rituximab treatment in pediatric-onset multiple sclerosis

Markus Breu  1 , Fredrik Sandesjö  2 , Ruxandra-Iulia Milos  3 , Jan Svoboda  4 , Jonatan Salzer  5 , Lisa Schneider  6 , Julian Benedikt Reichelt  1   7 , Annikki Bertolini  8 , Astrid Blaschek  9 , Katharina Fink  10 , Romana Höftberger  11   12 , Jan Lycke  13 , Kevin Rostásy  8 , Rainer Seidl  1 , Sandy Siegert  1 , Ronny Wickström  2 , Barbara Kornek  7   12
Affiliations
Multicenter Study

Rituximab treatment in pediatric-onset multiple sclerosis

Markus Breu et al. Eur J Neurol. 2024 May.

Abstract

Background and purpose: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce.

Methods: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed.

Results: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38-0.92) to 0.03 (95% CI 0.02-0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70-2.48) to 0.08 (95% CI 0.03-0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30-3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events.

Conclusion: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.

Keywords: central nervous system; cohort study; disease‐modifying therapy; pediatric‐onset multiple sclerosis; rituximab.

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Conflict of interest statement

MB received speaker honoraria from Sanofi‐Genzyme. JoS received institutional consultancy fees from Mabion SA. KF received lecture honoraria from Merck; has served on scientific advisory boards for Biogen, Novartis, Merck, Roche and Celgene. JL received lecture honoraria from Biogen, Novartis, Merck, Roche, Axelion, Sanofi, Celgene and BMS; has served on scientific advisory boards for Almirall, Biogen, Novartis, Merck, Roche, Celgene, BMS and Sanofi; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen and Novartis. KR received speaker honoraria from Merck and serves as a consultant for the Roche Operette2 trial. RW has served on scientific advisory boards for GW Pharma, Sobi and Octapharma, and has received speaker honoraria from Eisai and Sanofi. BK has received honoraria for speaking and participation in advisory boards from Biogen, BMS‐Celgene, Janssen, Merck, Novartis, Teva, Sanofi and Roche. FS, RM, JS, LS, JR, AB, AsB, RH, RS, SS report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Annualized relapse rate, new T2 lesions and CELs before and during treatment with rituximab (RTX) (annual rate; 95% confidence interval). Small dots represent individual patients.
FIGURE 2
FIGURE 2
EDSS before rituximab (RTX) start and on last follow‐up (median; 95% confidence interval).
FIGURE 3
FIGURE 3
Individual clinical courses of pediatric‐onset MS patients. Lines indicate the duration of follow‐up (in months) before DMT (dotted), under DMT other than RTX (dashed) and under RTX therapy. Arrows at the end of the lines indicate continued RTX therapy after the last follow‐up, squares indicate discontinuation of RTX therapy before the end‐of‐study or patients lost to follow‐up. Triangles indicate relapses, vertical lines indicate MRIs, and points indicate detection of T2 lesions (brain and/or spinal) or CELs (brain and/or spinal). Zero on the x‐axis indicates the start of RTX therapy. CEL, contrast‐enhancing MRI lesion; DMT, disease‐modifying therapy; MRI, magnetic resonance imaging; RTX, rituximab.
See this image and copyright information in PMC

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