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May 03, 2016; 86 (18) Article

Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort

Woo-Jin Lee, Soon-Tae Lee, Jung-Ick Byun, Jun-Sang Sunwoo, Tae-Joon Kim, Jung-Ah Lim, Jangsup Moon, Han Sang Lee, Yong-Won Shin, Keon-Joo Lee, Soyun Kim, Keun-Hwa Jung, Ki-Young Jung, Kon Chu, Sang Kun Lee
First published April 1, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002635
Woo-Jin Lee
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Soon-Tae Lee
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Jung-Ick Byun
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Jun-Sang Sunwoo
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Tae-Joon Kim
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Jung-Ah Lim
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Jangsup Moon
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Han Sang Lee
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Yong-Won Shin
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Keon-Joo Lee
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Soyun Kim
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Keun-Hwa Jung
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Ki-Young Jung
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Kon Chu
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Sang Kun Lee
From the Department of Neurology (W.-J.L., S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., S.K., K.-H.J., K.-Y.J., K.C., S.K.L.), Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital; and Program in Neuroscience (S.-T.L., J.-I.B., J.-S.S., T.-J.K., J.-A.L., J.M., H.S.L., Y.-W.S., K.-J.L., K.-H.J., K.-Y.J., K.C., S.K.L.), Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University; Department of Neurology (J.-I.B.), Kyung Hee University Hospital at Gangdong; Soonchunhyang University School of Medicine (J.-S.S.), Seoul, South Korea.
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Full PDF
Citation
Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort
Woo-Jin Lee, Soon-Tae Lee, Jung-Ick Byun, Jun-Sang Sunwoo, Tae-Joon Kim, Jung-Ah Lim, Jangsup Moon, Han Sang Lee, Yong-Won Shin, Keon-Joo Lee, Soyun Kim, Keun-Hwa Jung, Ki-Young Jung, Kon Chu, Sang Kun Lee
Neurology May 2016, 86 (18) 1683-1691; DOI: 10.1212/WNL.0000000000002635

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Abstract

Objective: To determine efficacy and safety of rituximab treatment as a second-line immunotherapy treatment for autoimmune limbic encephalitis (ALE) and to determine factors associated with functional improvement and favorable outcome following rituximab treatment.

Methods: We recruited 80 patients with ALE who were treated with rituximab as a second-line immunotherapy from the Korea Autoimmune Synaptic and Paraneoplastic Encephalitis Registry and reviewed 81 patients without rituximab as a control. We grouped patients according to the detection or type of antibodies; in addition, we evaluated clinical, laboratory, first-line immunotherapy, and rituximab treatment profiles and defined main outcomes as improvements on the modified Rankin Scale (mRS) score and a favorable mRS score (0–2) at the last follow-up.

Results: Functional improvement occurred more frequently in the rituximab group compared to the control group. In the rituximab group, 30 (37.5%) patients had synaptic autoantibodies, 15 (18.8%) in the paraneoplastic autoantibodies, and 35 (43.8%) were antibody-negative. The effect of rituximab was the same regardless of autoantibody status. Additional monthly rituximab therapy and partial response to first-line immunotherapies were associated with mRS score improvements, as well as favorable mRS scores. mRS scores of 4–6 as the worst neurologic status predicted an unfavorable mRS score. There were no reported serious infusion-related or infectious adverse effects of rituximab.

Conclusions: Rituximab is effective and safe as a second-line immunotherapy for ALE, regardless of autoantibody status. Additional monthly rituximab therapy might potentiate the efficacy of rituximab.

Classification of evidence: This study provides Class IV evidence that rituximab improves mRS scores for patients with autoimmune limbic encephalitis who fail first-line therapy.

GLOSSARY

ALE=
autoimmune limbic encephalitis;
CTCAE=
Common Terminology Criteria for Adverse Events;
IQR=
interquartile range;
IVIg=
IV immunoglobulin;
KASPER=
Korea Autoimmune-Synaptic and Paraneoplastic Encephalitis Registry;
mRS=
modified Rankin Scale;
NMDAR=
NMDA receptor;
SCLC=
small-cell lung cancer

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 1655

  • Supplemental data at Neurology.org

  • Received July 31, 2015.
  • Accepted in final form January 4, 2016.
  • © 2016 American Academy of Neurology
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