Rituximab in paediatric onset multiple sclerosis-a retrospective observational study

Introduction: Paediatric onset multiple sclerosis (POMS) is a severe disease with manifestation of physical disability and cognitive impairment at a young age. The chimeric anti-CD20 antibody rituximab (RTX) is frequently used off-label in multiple sclerosis (MS). However, studies in POMS are scarce. Objectives: To report the use of RTX in POMS. Methods: Retrospective review of all POMS patients who received RTX at the Medical University of Vienna between 11/1999 and 05/2021. All magnetic resonance imaging (MRI) scans were reassessed, and adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events v. 5.0. Outcome parameters were compared between RTX start and last follow-up (FU). This study was approved by the local ethics committee (1452/2020). Results: Overall, 23 patients (19 female, 10 treatment-naive) with a median age of 15.08 years at MS onset and 18.25 years at RTX initiation received a median (interquartile range (IQR)) of 4 (3-7) RTX infusions (375 mg/m2) during a median (IQR) FU duration of 25 (17-45) months. B cell depletion was successfully achieved in all patients. The median (IQR) annualized relapse rate decreased from 1.09 (0.31-2.4) to 0 (0-0) and the median (IQR) Expanded Disability Status Scale score improved from 1.5 (0-2.5) to 0 (0-1). The median (IQR) annualized rate of new T2 lesions decreased from 13.71 (5.56-60) to 0.55 (0-1.47) and gadolinium-enhancing lesions decreased from a median (IQR) of 1 (0-8.5) to 0 (0-0). Overall, 52% displayed no evidence of disease activity during RTX and most refractory activity was limited to the first 7 months and the first FU MRI. AEs were observed in 87% and were graded mild to moderate in most patients. However, 4 severe AEs occurred in a single patient who developed a prolonged B cell depletion (96 months) and hypogammaglobulinemia. Transient infusion reactions developed in 52% but decreased with subsequent infusions. Infections were recorded in 48% including two mild cases of COVID-19. Hypogammaglobulinemia was the most frequent laboratory abnormality in 55%. Only one patient discontinued RTX and was lost to FU after 20 months, due to non-medical reasons. Conclusions: RTX was generally safe and well tolerated in this cohort of 23 POMS patients. The high rate of hypogammaglobulinemia, however, represents a major long-term concern. Larger and prospective trials with a longer FU duration are required to further define the risk/benefit profile of RTX in POMS.