Publications by authors named "Meini Zhang"

5 Publications

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Low-dose rituximab treatment for new-onset generalized myasthenia gravis.

J Neuroimmunol 2021 Feb 24;354:577528. Epub 2021 Feb 24.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

The aim of this retrospective case series study was to evaluate the response and durability of rituximab in patients with new-onset acetylcholine receptor positive (AChR +) generalized myasthenia gravis (MG). Patients were initiated with low-dose rituximab treatment within 3.5 months of onset without concomitant oral immunosuppressants. Seventeen patients (89%) remained relapse-free with a mean follow-up of 51.3 months. Clinical improvement was observed in parallel with the maintenance of low-dose corticosteroids or the complete discontinuation of corticosteroids. Long-term depletion of B cells with low-dose rituximab treatment has shown favorable efficacy and tolerance in reducing disease activity for AChR+ generalized MG.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577528DOI Listing
February 2021

Immunotherapy choice and maintenance for generalized myasthenia gravis in China.

CNS Neurosci Ther 2020 12 26;26(12):1241-1254. Epub 2020 Oct 26.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.

Aims: To compare long-term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real-world settings.

Methods: This is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation.

Results: Among 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0-62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower-dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001).

Conclusions: Rituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.
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http://dx.doi.org/10.1111/cns.13468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702233PMC
December 2020

Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.

Lancet Neurol 2020 05;19(5):391-401

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD.

Methods: We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with highly relapsing NMOSD diagnosed according to 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, who had an Expanded Disability Status Scale (EDSS) score of 7·5 or lower, and had a history of at least two clinical relapses during the previous 12 months or three relapses during the previous 24 months with at least one relapse within the previous 12 months. Patients were randomly assigned (1:1) to intravenous tocilizumab (8 mg/kg every 4 weeks) or oral azathioprine (2-3 mg/kg per day) by an independent statistician using computer-generated randomisation software with permuted blocks of four. The central review committee, EDSS raters, laboratory personnel, and radiologists were masked to the treatment assignment, but investigators and patients were aware of treatment allocation. The minimum planned duration of treatment was 60 weeks following randomisation. The primary outcome was time to first relapse in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, and the per-protocol population, which included all patients who used azathioprine or tocilizumab as monotherapy. For the analyses of the primary outcome, the patients were prespecified into two subgroups according to concomitant autoimmune disease status. Safety was assessed in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03350633.

Findings: Between Nov 1, 2017, and Aug 3, 2018, we enrolled 118 patients, of whom 59 were randomly assigned to tocilizumab and 59 were randomly assigned to azathioprine. All 118 patients received one dose of study drug and were included in the full analysis set. 108 participants were included in the per-protocol analysis (56 in the tocilizumab group and 52 in the azathioprine group). In the full analysis set, median time to the first relapse was longer in the tocilizumab group than the azathioprine group (78·9 weeks [IQR 58·3-90·6] vs 56·7 [32·9-81·7] weeks; p=0·0026). Eight (14%) of 59 patients in the tocilizumab group and 28 (47%) of 59 patients in the azathioprine group had a relapse at the end of the study (hazard ratio [HR] 0·236 [95% CI 0·107-0·518]; p<0·0001). In the per-protocol analysis, 50 (89%) of 56 patients in the tocilizumab group were relapse-free compared with 29 (56%) of 52 patients in the azathioprine group at the end of the study (HR 0·188 [95% CI 0·076-0·463]; p<0·0001); the median time to first relapse was also longer in the tocilizumab group than the azathioprine group (67·2 weeks [IQR 47·9-77·9] vs 38·0 [23·6-64·9]; p<0·0001). In the prespecified subgroup analysis of the full analysis set stratified by concomitant autoimmune diseases, among patients without concomitant autoimmune diseases, three (9%) of 34 patients in the tocilizumab group and 13 (35%) of 37 patients in the azathioprine group had relapsed by the end of the study. Among patients with concomitant autoimmune diseases, a lower proportion of patients in the tocilizumab group had a relapse than in the azathioprine group (five [20%] of 25 patients vs 15 [68%] of 22 patients; HR 0·192 [95% CI 0·070-0·531]; p=0·0004). 57 (97%) of 59 patients in the tocilizumab group and 56 (95%) of 59 patients in the azathioprine group had adverse events. Treatment-associated adverse events occurred in 36 (61%) of 59 tocilizumab-treated patients and 49 (83%) of 59 azathioprine-treated patients. One death (2%) occurred in the tocilizumab group and one (2%) in the azathioprine group, but neither of the deaths were treatment-related.

Interpretation: Tocilizumab significantly reduced the risk of a subsequent NMOSD relapse compared with azathioprine. Tocilizumab might therefore be another safe and effective treatment to prevent relapses in patients with NMOSD.

Funding: Tianjin Medical University, Advanced Innovation Center for Human Brain Protection, National Key Research and Development Program of China, National Science Foundation of China.
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http://dx.doi.org/10.1016/S1474-4422(20)30070-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935423PMC
May 2020

Alteration of Circadian Rhythms in 2D2 Transgenic Mice.

Med Sci Monit 2018 Nov 17;24:8272-8278. Epub 2018 Nov 17.

Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China (mainland).

BACKGROUND Several immunological functions are dependent on circadian rhythms. However, there are still relatively few studies about circadian rhythms in neuromyelitis optica spectrum disorders (NMOSD) and 2D2 transgenic mice. We explore whether 2D2 mice have abnormalities in circadian rhythms and the potential underlying molecular mechanism. MATERIAL AND METHODS We first observed the wheel-running motion of the control and 2D2 mice using wheel-running measurements. The cytokine levels were also analyzed using enzyme-linked immunosorbent assay (ELISA), and the results of clock gene expressions in the suprachiasmatic nucleus (SCN) were investigated using real-time polymerase chain reaction (real-time PCR). RESULTS The wheel-running rhythm in 2D2 mice differed from that of the controls. The TNF-α and IL-10 rhythms were disrupted in 2D2 mice. Additionally, the rhythm of the clock genes, Per1 and Per2, and expression in the SCN of 2D2 mice were also changed. CONCLUSIONS The results presented here indicate that alteration of circadian rhythms in 2D2 mice affects behavior and immune function, and the potential molecular mechanism might be the Per1 and Per2 expression disorders in the SCN. 2D2 mice might be a suitable model for studying circadian disruption in NMOSD.
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http://dx.doi.org/10.12659/MSM.908528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252048PMC
November 2018

Effectiveness of low dose of rituximab compared with azathioprine in Chinese patients with neuromyelitis optica: an over 2-year follow-up study.

Acta Neurol Belg 2017 Sep 12;117(3):695-702. Epub 2017 Jun 12.

Department of Neurology, First Hospital of Shanxi Medical University, No. 85 Jiefangnan Road, Taiyuan, 030001, Shanxi, China.

Neuromyelitis optical (NMO) and neuromyelitis optical spectrum disorder (NMOSD) are inflammatory autoimmune demyelination diseases affecting the central nervous system. We investigated the efficiency of low-dose rituximab treatment in 31 Chinese patients with NMO/NMOSD across a median period of 2.29 ± 0.97 years and azathioprine combined with corticosteroid treatment in 34 Chinese patients with NMO/NMOSD across a median period of 2.61 ± 0.94 years. Among the rituximab-treated patients, the mean Expanded Disability Status Scale (EDSS) was 5.62 ± 1.35 before treatment and 4.48 ± 0.78 at last follow-up, and the mean annualized relapse rate (ARR) was 1.39 ± 0.42 before treatment and 0.03 ± 0.13 at last follow-up. Among the azathioprine-treated patients, the mean EDSS was 5.63 ± 1.29 before treatment and 5.05 ± 1.00 at last follow-up, and the mean ARR was 1.28 ± 0.34 before treatment and 0.49 ± 0.21 at last follow-up. In this study, we showed that using low-dosage rituximab could benefit Chinese patients with NMO by reducing the new occurrence of relapses dramatically. Compared with the azathioprine-treated patients, we concluded that rituximab is more effective in preventing NMO relapse and could improve the symptoms.
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http://dx.doi.org/10.1007/s13760-017-0795-6DOI Listing
September 2017