Rituximab shows second-line promise in autoimmune limbic encephalitis

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By Lucy Piper

Rituximab is an effective and well-tolerated second-line treatment for patients with autoimmune limbic encephalitis (ALE), suggests research.

The findings, published in Neurology, show that the immunotherapy significantly improved modified Rankin Scale (mRS) scores in 76.3% of 80 patients with ALE and 68.8% achieved a favourable mRS score, of 0-2, an average of 22.5 months later.

The patients had already received first-line immunotherapy a median 6.8 months after symptom onset, at which point the median mRS score was 3. And although 31.3% showed partial responses to this treatment, their symptoms continued to deteriorate and by the time rituximab was administered an average of 12.1 months after symptom onset, the average mRS score was 4.

Following a median rituximab cycle of 5 weeks, the patients had a median mRS score at last follow-up of 2.

Researcher Kon Chu (Seoul National University, South Korea) and colleagues highlight that rituximab treatment was effective regardless of autoantibody status. Among the patients, 37.5% had synaptic autoantibodies, 18.8% paraneoplastic autoantibodies and 43.8% were antibody-negative.

"Therefore, rituximab administration could be considered in clinically diagnosed ALE without demonstrated autoantibody after an insufficient response to first-line immunotherapies", they say.

When compared with a control group of 81 ALE patients who received first-line immunotherapies but not rituximab, the rituximab-treated patients showed significantly more mRS improvement, although they did not achieve more favourable mRS scores.

Grouping the 161 patients according to whether or not they achieved at least a partial response to first-line therapy showed higher rates of favourable outcome among the 79 who did, but rates were similar for those receiving and not receiving rituximab, at 88.0% and 83.3%, respectively.

On multivariate analysis, partial response to first-line immunotherapy was associated with a significant 9.5-fold increased chance of mRS improvement, which the researchers believe is likely to be an effect of rituximab rather than a delayed effect of the first-line treatment given the lag between the two.

"This might be explained by some common mechanisms in ameliorating autoimmunity shared by the first-line immunomodulators and rituximab", they suggest.

By contrast among the 82 patients who did not respond to first-line immunotherapy, rates of favourable outcomes were lower but occurred more frequently in those who went on to receive rituximab, at 60.0% versus 22.2%.

Chu and team therefore propose that rituximab "might be considered as a first-line immunotherapy for ALE".

Receiving additional monthly rituximab cycles also significantly increased the likelihood of achieving a favourable mRS score 5.2-fold, whereas an mRS score at the worst neurological status was associated with unfavourable mRS scores.

Rituximab was generally well tolerated, with infectious complications occurring at a similar rate to those previously reported for patients with ALE treated with other immunotherapies, and there was no evidence of opportunistic infections.

But in a linked editorial, Timothy Vollmer (University of Colorado School of Medicine, Aurora, USA) and Micheline McCarthy (University of Miami, Florida) point out that the dose and treatment regimen in the current study was not standardised and varied widely, so further study is needed to identify optimal treatment.

"Nevertheless, this is one of the largest case series focused on treatment and outcomes in [ALE] reported to date and, as in other such studies, suggests rituximab may have an important role in the treatment of [ALE], particularly if [ALE] is diagnosed and treated early", they say.

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