Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study

Abstract

A considerable portion of autoimmune encephalitis (AE) does not respond to conventional immunotherapies and subsequently has poor outcomes. We aimed to determine the efficacy of tocilizumab, an anti-interleukin-6 antibody, in rituximab-refractory AE compared with other treatment options. From an institutional cohort of AE, 91 patients with inadequate clinical response to first-line immunotherapy and following rituximab were retrospectively reviewed. Patients were grouped according to their further immunotherapy strategies. Thirty (33.0 %) patients were included in the tocilizumab group, 31 (34.0 %) in the additional rituximab group, and 30 (33.0 %) in the observation group. Outcomes were defined as the favorable modified Rankin Scale scores (≤2) at 1 and 2 months from the initiation of each treatment strategy and at the last follow-up. Favorable clinical response (improvement of the modified Rankin Scale scores by ≥ 2 points or achievement of the mRS scores ≤ 2) at the last follow-up was also analyzed. The tocilizumab group showed more frequent favorable mRS scores at 2 months from treatment initiation and at the last follow-up compared with those at the relevant time points of the remaining groups. The majority (89.5 %) of the patients with clinical improvement at 1 month from tocilizumab treatment maintained a long-term favorable clinical response. No serious adverse effects of rituximab or tocilizumab were reported. Therefore, we suggest that tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab. The tocilizumab-mediated clinical improvement manifests as early at 1 month after treatment initiation.

Bortezomib treatment for severe refractory anti‐NMDA receptor encephalitis

“…All patients received tocilizumab after second‐line immunotherapy for at least three cycles (median [range], 4 [3–8] cycles). According to our previous report, patients who responded to tocilizumab showed mRS improvement within 1–2 months (cycles) after tocilizumab therapy 5. However, all the patients remained vegetative and demonstrated the accompanying movement symptoms, including oromandibular dyskinesia, stereotypic limb movements, rigidity, and/or abnormal posture.…”

“…A commercial indirect fluorescence assay (Euroimmun AG, Lübeck, Germany) was used to screen for antibodies to the NMDAR, leucine‐rich glioma inactivated‐1, contactin‐associated protein‐like 2, α ‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) 1, AMPA2, and γ ‐aminobutyric‐acid type B, as previously described 5. Classic paraneoplastic autoantibodies, such as anti‐Hu, ‐Yo, ‐Ri, ‐CV2, ‐Ma2, ‐amphiphysin, ‐recoverin, ‐SOX1, and ‐titin were also screened using the immunoblotting method (Euroimmun).…”

“…Anti‐glutamic acid decarboxylase (GAD) antibody levels were measured by radioimmunoassay (RSR Limited, Cardiff, UK), as previously described 15. Possible infectious etiologies were excluded according to a protocol previously described 5. Diagnosis of anti‐NMDAR encephalitis was made according to the expert consensus criteria 16.…”

“…Although most patients with autoimmune encephalitis respond to immunotherapy,1, 2, 3 a small, but significant, number of patients show an insufficient response even after aggressive immunotherapy; therefore, several treatment options are being explored 4, 5, 6. Long‐lived plasma cells that can survive without cell division and continuously secrete autoantibodies are considered to contribute to the poor clinical course in the patients, given their known resistance to B‐cell depleting agents, conventional immunosuppressants, and antiproliferative agents 7…”

Interleukin-6 Blockade as Rescue Therapy in Autoimmune Encephalitis

“…The study in this issue of Neurotherapeutics by Lee et al [7] describes the use of the monoclonal antibody tocilizumab [an interleukin (IL)-6 blocker] in patients with AE who have failed to respond to rituximab and continue to have significant impairments. In this retrospective institutional cohort study, carried out over a 3-year period, of 185 patients with suspected and definite AE, 91 patients had received first-line therapy and rituximab yet had persistent neurologic deficits 1 month after rituximab.…”