When can improvement be expected after administering rituximab (rituximab) for seronegative autoimmune encephalitis?

From the Guidelines

Improvement after administering rituximab for seronegative autoimmune encephalitis can be expected within 2-8 weeks, with some patients showing significant response up to 3-6 months after treatment. The standard rituximab regimen consists of 375 mg/m² weekly for 4 weeks, or two 1000 mg doses given two weeks apart, as recommended in the 2021 study published in the Journal of Neurology, Neurosurgery and Psychiatry 1. Response time varies considerably between patients due to differences in blood-brain barrier permeability, disease severity, and individual immune system characteristics.

Key Considerations

• While waiting for rituximab to take effect, clinicians often use concurrent therapies such as corticosteroids, plasma exchange, or intravenous immunoglobulin to provide more immediate symptom relief.
• Rituximab works by depleting B cells, which are responsible for antibody production, but this mechanism takes time to affect the autoimmune process in the brain.
• Regular monitoring of clinical symptoms, neurological examination, and sometimes follow-up imaging or EEG is essential to assess treatment response, as outlined in the best practice recommendations for acute management of autoimmune encephalitis 1.
• Some patients may require maintenance rituximab infusions every 6 months if they respond well initially but experience symptom recurrence.

Treatment Approach

• The decision to start rituximab should be based on the clinical suspicion of autoimmune encephalitis and the presence of a clinically relevant antibody, as suggested in the 2021 study 1.
• If there is no clear objective or subjective evidence of improvement with conventional second-line therapies, consideration of novel approaches such as tocilizumab or bortezomib may be necessary, although the evidence to support their use is limited 1.

From the Research

Improvement Timeline for Seronegative Autoimmune Encephalitis with Rituximab

• Improvement in seronegative autoimmune encephalitis after administering rituximab can be expected to vary based on several factors including the timing of treatment initiation, the specific subtype of autoimmune encephalitis, and the patient's overall health status 2, 3, 4, 5, 6.
• Studies suggest that early initiation of rituximab treatment (≤3 months) may achieve better improvements in clinical outcomes, such as the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score and the modified Rankin Scale (mRS) score 2, 4.
• Significant improvements in CASE scores and marked acceleration in recovery have been observed in patients treated with a combined low-dose rituximab regimen, with improvements persisting even after 1 year 2.
• A meta-analysis has shown that good functional outcomes (mRS ≤2) occur in approximately 72.2% of patients following rituximab therapy, with a mean mRS score decrease of 2.67, indicating substantial improvement 3.
• Real-world evidence from the GENERATE registry indicates that rituximab treatment is associated with improved outcomes in patients with NMDAR-, LGI1-, and CASPR2-AE, with earlier treatment initiation leading to better long-term improvements 4.
• In seronegative autoimmune encephalitis, the frequency of achieving a good 2-year outcome (modified Rankin scale 0-2) was 56.5%, with any immunotherapy, including rituximab, associated with clinical improvement in patients with low risk for poor 2-year outcomes 5.
• Survival analysis has demonstrated that rituximab use is associated with a lower hazard for time to first relapse and recurring relapses in both pediatric and adult patients with autoimmune encephalitis, highlighting its benefit in reducing relapse rates 6.

Factors Influencing Improvement

• Early treatment initiation (≤3 months) is associated with better long-term improvements 2, 4.
• The specific subtype of autoimmune encephalitis, such as NMDAR-, LGI1-, or CASPR2-AE, may influence the effectiveness of rituximab treatment 4.
• Patient's overall health status, including the presence of refractory status epilepticus, age of onset, and delay of immunotherapy, can impact the outcome of rituximab treatment 5.
• Combination immunotherapy, including steroid, immunoglobulin, rituximab, and tocilizumab, may be associated with better outcomes in patients with high risk for poor 2-year outcomes 5.