Ying Du1, Chao Zhao1, Juntong Liu1, Chuan Li1, Qi Yan1, Lin Li1, Yunfeng Hao1, Dan Yao1, Huaxing Si1, Yingjun Zhao2, Wei Zhang3. 1. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an City, 710038, Shaanxi Province, China. 2. Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, 361005, China. yjzhao@xmu.edu.cn. 3. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an City, 710038, Shaanxi Province, China. tdzw@fmmu.edu.cn.
Abstract
BACKGROUND: Autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) presents pathogenesis mediated by B cell-secreting antibodies. Rituximab is a second-line choice for the treatment for AE with NSAbs, which can cause B cell depletion via targeting CD20. However, the optimal protocol and dosage of rituximab combined with first-line therapy for NSAbs-associated AE remains unclear so far. In this study, we explored the efficacy and safety of low-dose rituximab combined with first-line treatment for NSAbs-associated AE. METHODS: Fifty-nine AE patients with NSAbs were enrolled, and retrospectively divided into common first-line therapy (41 patients) and combined low-dose rituximab (100 mg induction weekly with 3 circles, followed by 100 mg reinfusion every 6 months) with first-line therapy (18 patients). Outcome measures included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score (primary endpoint), changes in the modified Rankin Scale (mRS), the Mini-mental State Examination (MMSE), the patient and caregiver Neuropsychiatric Inventory (NPI) score at each visit (baseline, discharge, 6 months, 12 months and last follow-up) between two groups (secondary endpoint), as well as oral prednisone dosage, relapse and adverse effects during follow-up. RESULTS: Compared with traditional first-line therapy group, for primary outcome, CASE scores at last follow-up were significantly improved in combined rituximab group, as well as markedly improving changes of CASE scores between baseline and each visit. While changes of mRS, MMSE and NPI scores, as secondary endpoint, were all markedly accelerating improvement between baseline and each visit, as well as both oral prednisone dosage and relapse were also greatly reduced during follow-up. Meanwhile, longitudinal analysis in combination of rituximab cohort also revealed persistently marked amelioration in a series of scales from baseline even more than 1 year. Moreover, analysis in rituximab subgroup showed no difference in any clinical outcomes between combination with single first-line and with repeated first-line treatment (≥ 2 times), while compared to delayed combination with rituximab (> 3 months), early initiation of combination (≤ 3 months) might achieve better improvements in CASE and MMSE assessment even 1 year later. No rituximab-correlated serious adverse events have been reported in our patients. CONCLUSIONS: Our simplified regimen of combined low-dose rituximab firstly showed significantly accelerating short-term recovery and long-term improvement for AE with NSAbs, in parallel with markedly reduced prednisone dosage and clinical relapses. Moreover, opportunity of protocol showed earlier initiation (≤ 3 months) with better long-term improvement.
BACKGROUND: Autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) presents pathogenesis mediated by B cell-secreting antibodies. Rituximab is a second-line choice for the treatment for AE with NSAbs, which can cause B cell depletion via targeting CD20. However, the optimal protocol and dosage of rituximab combined with first-line therapy for NSAbs-associated AE remains unclear so far. In this study, we explored the efficacy and safety of low-dose rituximab combined with first-line treatment for NSAbs-associated AE. METHODS: Fifty-nine AE patients with NSAbs were enrolled, and retrospectively divided into common first-line therapy (41 patients) and combined low-dose rituximab (100 mg induction weekly with 3 circles, followed by 100 mg reinfusion every 6 months) with first-line therapy (18 patients). Outcome measures included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score (primary endpoint), changes in the modified Rankin Scale (mRS), the Mini-mental State Examination (MMSE), the patient and caregiver Neuropsychiatric Inventory (NPI) score at each visit (baseline, discharge, 6 months, 12 months and last follow-up) between two groups (secondary endpoint), as well as oral prednisone dosage, relapse and adverse effects during follow-up. RESULTS: Compared with traditional first-line therapy group, for primary outcome, CASE scores at last follow-up were significantly improved in combined rituximab group, as well as markedly improving changes of CASE scores between baseline and each visit. While changes of mRS, MMSE and NPI scores, as secondary endpoint, were all markedly accelerating improvement between baseline and each visit, as well as both oral prednisone dosage and relapse were also greatly reduced during follow-up. Meanwhile, longitudinal analysis in combination of rituximab cohort also revealed persistently marked amelioration in a series of scales from baseline even more than 1 year. Moreover, analysis in rituximab subgroup showed no difference in any clinical outcomes between combination with single first-line and with repeated first-line treatment (≥ 2 times), while compared to delayed combination with rituximab (> 3 months), early initiation of combination (≤ 3 months) might achieve better improvements in CASE and MMSE assessment even 1 year later. No rituximab-correlated serious adverse events have been reported in our patients. CONCLUSIONS: Our simplified regimen of combined low-dose rituximab firstly showed significantly accelerating short-term recovery and long-term improvement for AE with NSAbs, in parallel with markedly reduced prednisone dosage and clinical relapses. Moreover, opportunity of protocol showed earlier initiation (≤ 3 months) with better long-term improvement.
Authors: Franziska S Thaler; Luise Zimmermann; Stefan Kammermeier; Christine Strippel; Marius Ringelstein; Andrea Kraft; Kurt-Wolfram Sühs; Jonathan Wickel; Christian Geis; Robert Markewitz; Christian Urbanek; Claudia Sommer; Kathrin Doppler; Loana Penner; Jan Lewerenz; Rosa Rößling; Carsten Finke; Harald Prüss; Nico Melzer; Klaus-Peter Wandinger; Frank Leypoldt; Tania Kümpfel Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-10-01