Effectiveness of Anti-CD20 B cells depleting therapy versus conventional treatment in severe Anti-N-methyl-d-aspartate receptor encephalitis: A real-world multi-center prospective cohort study

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Approximately 25 ​%-40 ​% of anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) patients develop refractory disease with prolonged neurological deficits. We aim to evaluate the efficacy of B cell depletion therapy (BCDT) via CD20 antibodies versus conventional first-line immunotherapy only (intravenous methylprednisolone for 5 days, 0.4 ​g/kg intravenous immunoglobulin for 5 days, and ≥4 consecutive plasma exchange treatments, non-BCDT group) in treatment of severe NMDARE in the real-world setting. From multicenter cohort of severe NMDARE, 108 patients (ofatumumab group 36; rituxixmab group 36; non-BCDT group 36) were prospectively reviewed. The primary end point was the proportion of patients to achieving good outcomes (modified Rankin Scale scores ≤2) at 3 months. Secondary end points included longitudinal outcomes assessed by mRS scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores, cognitive function and adverse events (AEs). BCDT demonstrated a higher frequency of mRS scores ≤2 compared to non-BCDT at 3 months (ofatumumab 63.9 ​% vs. non-BCDT 36.1 ​%, p ​< ​0.001; rituximab 55.6 ​% vs. non-BCDT 36.1 ​%, p ​= ​0.007, respectively). Ofatumuamb showed superior therapeutic response at 1 month compared to both rituximab-treated patients (mean CASE score: 5.89 vs 7.91, p ​= ​0.025) and non-BCDT treated patients (mean CASE score: 5.89 vs 9.97, p ​< ​0.0001). All groups improved over 12 months, with significantly higher complete remission rates in BCDT groups (70.8 ​%-75 ​% vs. 55.6 ​%, p ​< ​0.05). Five of 33 patients (15.2 ​%) experienced persistent mild cognitive impairment. AEs were mild-to moderate in severity. We calculated the probability of relapse-free as ofatumumab and rituximab reduced risk of disease relapses compared to non-BCDT (ofatumumab vs. non-BCDT: HR, 0.193; 95 ​% CI, 0.062-0.6; p ​= ​0.007; rituximab vs. non-BCDT: HR, 0.265; 95 ​% CI, 0.089-0.787; p ​= ​0.029). Therefore, we suggest that BCDT effectively promoted neurological recovery, and reduced relapse risk with favorable safety, while ofatumumab demonstrated superior efficacy in controlling early disease severity.

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