The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In any case, the long-term persistence of (re-)activatable autoantigen-specific ThEx cells in patients in remission may well explain the less-than-perfect treatment efficacy of steroid-sparing agents, 64-67 depletion of CD19/CD20 memory B cells, 68,69 as well as exacerbation of disease by b -IFN. 27,70”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [66]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders
Wingerchuk, D. M., Banwell, B., Bennett, J. L., Cabre, P., Carroll, W., Chitnis, T., de Seze, J., Fujihara, K., Greenberg, B., Jacob, A., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001729 · Cited by 4,649
Self-citationAn Approximate Distribution of Estimates of Variance Components
Satterthwaite, F. E. (1946) · Biometrics Bulletin · doi:10.2307/3002019 · Cited by 4,373
A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis
Lennon, V. A., Wingerchuk, D. M., Kryzer, T. J., Pittock, S. J., Lucchinetti, C. F., Fujihara, K., Nakashima, I., & Weinshenker, B. G. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17551-x · Cited by 3,239
The spectrum of neuromyelitis optica
Wingerchuk, D. M., Lennon, V. A., Lucchinetti, C. F., Pittock, S. J., & Weinshenker, B. G. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70216-8 · Cited by 2,182
Targeting Interleukin-6 Signaling in Clinic
Kang, S., Tanaka, T., Narazaki, M., & Kishimoto, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.026 · Cited by 904
Eculizumab in Aquaporin-4–Positive Neuromyelitis Optica Spectrum Disorder
Pittock, S. J., Berthele, A., Fujihara, K., Kim, H. J., Levy, M., Palace, J. A., Nakashima, I., Terzi, M., Totolyan, N. A., Viswanathan, S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1900866 · Cited by 887
Cree, B. A. C., Bennett, J. L., Kim, H. J., Weinshenker, B. G., Pittock, S. J., Wingerchuk, D. M., Fujihara, K., Paul, F., Cutter, G. R., Marignier, R., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31817-3 · Cited by 756
Self-citationEULAR recommendations for the management of Sjogren's syndrome with topical and systemic therapies
Ramos-Casals, M., Brito-Zerón, P., Bombardieri, S., Bootsma, H., De Vita, S., Dörner, T., Fisher, B. A., Gottenberg, J.-E., Hernandez-Molina, G., Kocher, A., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-216114 · Cited by 732
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
Yamamura, T., Kleiter, I., Fujihara, K., Palace, J. A., Greenberg, B. M., Zakrzewska‐Pniewska, B., Patti, F., Tsai, C., Saiz, A., Yamazaki, H., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1901747 · Cited by 663
Neuromyelitis Optica Study Group (NEMOS), Trebst, C., Jarius, S., Berthele, A., Paul, F., Schippling, S., Wildemann, B., Borisow, N., Kleiter, I., Aktas, O., et al. (2014) · Journal of Neurology · doi:10.1007/s00415-013-7169-7 · Cited by 595
Cited by
Sorted by citations
Jarius, S., Paul, F., Weinshenker, B. G., Levy, M., Kim, H. J., & Wildemann, B. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0214-9 · Cited by 503
Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies
Contentti, E. C., & Correale, J. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02249-1 · Cited by 347
Diagnosis and classification of optic neuritis
Petzold, A., Fraser, C. L., Abegg, M., Alroughani, R., Alshowaeir, D., Alvarenga, R., Andris, C., Asgari, N., Barnett, Y., Battistella, R., et al. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00200-9 · Cited by 330
“15 Relapsing optic neuritis that is of autoimmune cause will require long-term immunomodulation or suppression.”
Interleukin 6: at the interface of human health and disease
Grebenciucova, E., & VanHaerents, S. A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1255533 · Cited by 326
Kümpfel, T., Giglhuber, K., Aktaş, O., Ayzenberg, I., Bellmann–Strobl, J., Häußler, V., Havla, J. B., Hellwig, K., Hümmert, M. W., Jarius, S., et al. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11910-z · Cited by 263
“In case of therapy failure with rituximab, a combination therapy, tocilizumab, or other experimental therapies may be considered.”
BackgroundNeutrophil diversity and function in health and disease
Zhang, F., Xia, Y., Su, J., Quan, F., Zhou, H., Li, Q., Feng, Q., Lin, C., Wang, D., & Jiang, Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02049-y · Cited by 306
Neuromyelitis Optica Spectrum Disorder
Wingerchuk, D. M., & Lucchinetti, C. F. (2022) · New England Journal of Medicine · doi:10.1056/nejmra1904655 · Cited by 220
Targeted Immunotherapy for Autoimmune Disease
Jung, S. M., & Kim, W. (2022) · Immune Network · doi:10.4110/in.2022.22.e9 · Cited by 191
“Recently, therapeutic application of anti-IL-6 therapy has been investigated in SLE, neuromyelitis optica, and systemic sclerosis (17,57,58).”
BackgroundRingelstein, M., Ayzenberg, I., Lindenblatt, G., Fischer, K., Gahlen, A., Novi, G., Hayward-Koennecke, H. K., Schippling, S., Rommer, P. S., Kornek, B., et al. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001100 · Cited by 160
Bruijstens, A. L., Wendel, E., Lechner, C., Bartels, F., Finke, C., Breu, M., Flet‐Berliac, L., de Chalus, A., Adamsbaum, C., Capobianco, M. A. N., et al. (2020) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2020.10.005 · Cited by 160
New therapies for neuromyelitis optica spectrum disorder
Levy, M., Fujihara, K., & Palace, J. A. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30392-6 · Cited by 151
Multiple sclerosis and related disorders
Goodin, D. G. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780198869696.003.0006 · Cited by 143
Hope for patients with neuromyelitis optica spectrum disorders — from mechanisms to trials
Pittock, S. J., Ζεκερίδου, Α., & Weinshenker, B. G. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00568-8 · Cited by 148
NMOSD and MOGAD: an evolving disease spectrum
Uzawa, A., Oertel, F. C., Mori, M., Paul, F., & Kuwabara, S. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-01014-1 · Cited by 128
“In the TANGO study, an open-label, multicentre, randomized, phase II trial, tocilizumab reduced the risk of relapses compared with azathioprine in people with highly relapsing NMOSD 211 .”
Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction
Gryka-Marton, M., Grabowska, A. D., & Szukiewicz, D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083532 · Cited by 142
“Monoclonal antibodies, such as tocilizumab and sartral-izumab, have demonstrated efficacy in stabilizing BBB integrity, reducing inflammation-driven neurological damage, and preventing immune cell infiltration into the CNS [203,204].”
Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies
Yasmeen, F., Pirzada, R. H., Ahmad, B., Choi, B., & Choi, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147666 · Cited by 131
“IL-1 is a dominant regulator of inflammation by regulating a diversity of innate immune mechanisms [179].”
BackgroundUpdates in NMOSD and MOGAD Diagnosis and Treatment
Cacciaguerra, L., & Flanagan, E. P. (2023) · Neurologic Clinics · doi:10.1016/j.ncl.2023.06.009 · Cited by 112
Contentti, E. C., Rojas, J. I., Cristiano, E., Marques, V. D., Flores-Rivera, J. D. J., Lana–Peixoto, M. A., Navas, C., Alvarenga, R. M. P., Sato, D. K., de Castillo, I. S., et al. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102428 · Cited by 88
“Tocilizumab (anti-IL-6R) has been shown to significantly reduce the risk of new relapses, in comparison with AZA (Zhang et al., 2020).”
Aletaha, D., Kerschbaumer, A., Kastrati, K., Dejaco, C., Dougados, M., McInnes, I. B., Sattar, N. A., Stamm, T., Takeuchi, T., Trauner, M., et al. (2022) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2022-222784 · Cited by 85
“148 150;151 Safety considerations with other biological IL-6 pathway inhibitors.”
Saggau, C., Bacher, P., Esser, D., Rasa, M., Meise, S., Mohr, N., Kohlstedt, N., Hutloff, A., Schacht, S.-S., Dargvainiene, J., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.08.005 · Cited by 79
Tian, D., Li, Z., Yuan, M., Zhang, C., Gu, H., Wang, Y., & Shi, F. (2020) · The Lancet Regional Health - Western Pacific · doi:10.1016/j.lanwpc.2020.100021 · Cited by 75
Self-citationA comprehensive review of the advances in neuromyelitis optica spectrum disorder
Siriratnam, P., Huda, S., Butzkueven, H., van der Walt, A., Jokubaitis, V., & Monif, M. (2023) · Autoimmunity Reviews · doi:10.1016/j.autrev.2023.103465 · Cited by 81
Ma, X., Kermode, A. G., Hu, X., & Qiu, W. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102522 · Cited by 63
Self-citationYamamura, T., Weinshenker, B. G., Yeaman, M. R., Seze, J. D., Patti, F., Lobo, P., von Büdingen, H.-C., Kou, X., Weber, K., & Greenberg, B. M. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104025 · Cited by 63
Antibody Therapies in Autoimmune Encephalitis
Smets, I., & Titulaer, M. J. (2022) · Neurotherapeutics · doi:10.1007/s13311-021-01178-4 · Cited by 61
Treatment of Neuromyelitis Optica Spectrum Disorders
Chan, K., & Lee, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168638 · Cited by 67
“Tocilizumab is a potentially effective and safe treatment for relapse prevention in NMOSD [82].”
BackgroundGospe, S. M., Chen, J. J.-W., & Bhatti, M. T. (2020) · Eye · doi:10.1038/s41433-020-01334-8 · Cited by 60
Double-negative neuromyelitis optica spectrum disorder
Wu, Y. T., Geraldes, R., Juryńczyk, M., & Palace, J. A. (2023) · Multiple Sclerosis Journal · doi:10.1177/13524585231199819 · Cited by 57
“50 Tocilizumab (TCZ, an anti-IL-6 receptor monoclonal antibody (mAb)) showed some promise in a couple of studies; however, they were either small and only subanalyzed AQP4-IgG-negative NMOSD rather than DN NMOSD patients Tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorders: to GO…”
Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder
Holmøy, T., Høglund, R. A., Illés, Z., Myhr, K., & Torkildsen, Ø. (2020) · Journal of Neurology · doi:10.1007/s00415-020-10235-5 · Cited by 55
Rigal, J., Pugnet, G., Ciron, J., Lepine, Z., & Biotti, D. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102483 · Cited by 53
Update on neuromyelitis optica spectrum disorder
Holroyd, K. B., Manzano, G. S., & Levy, M. (2020) · Current Opinion in Ophthalmology · doi:10.1097/icu.0000000000000703 · Cited by 53
“Tocilizumab treated patients also showed a decrease in serum anti-AQP4 IgG titers [63].”
BackgroundResultInfluentialTargeting cytokine networks in neuroinflammatory diseases
Becher, B., Derfuss, T. J., & Liblau, R. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01026-y · Cited by 56
“Tocilizumab, another IL-6R-blocking antibody, also showed favourable effects in NMOSD in a phase II trial from China 143 .”
B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
Zhang, C., Zhang, T., Liu, Y., Jia, D., Zeng, P., Chen, D., Yuan, M., Liu, Q., Wang, Y., & Shi, F. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001070 · Cited by 52
Self-citationRole of Serum IL‐6 in Neuropsychiatric Systemic lupus Erythematosus
Hirohata, S., & Kikuchi, H. (2021) · ACR Open Rheumatology · doi:10.1002/acr2.11217 · Cited by 50
Monoclonal Antibody Therapies Beyond Complement for NMOSD and MOGAD
Redenbaugh, V., & Flanagan, E. P. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01206-x · Cited by 50
“is an open-label, multicenter, randomized, phase 2 trial for tocilizumab in NMOSD [136].”
BackgroundShi, M., Chu, F., Jin, T., & Zhu, J. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13836 · Cited by 50
Neonatal Fc Receptor–Targeted Therapies in Neurology
Nelke, C., Spatola, M., Schroeter, C. B., Wiendl, H., & Lünemann, J. D. (2022) · Neurotherapeutics · doi:10.1007/s13311-021-01175-7 · Cited by 48
“Many therapeutic mAbs have proven efficacious for a number of neurological indications, i.e. Eculizumab inhibits complement activation in MG by inhibiting C5 [75], while Tocilizumab targets IL-6 for treatment of NMSOD [85].”
BackgroundInfluentialKastrati, K., Aletaha, D., Burmester, G. R., Chwala, E., Dejaco, C., Dougados, M., McInnes, I. B., Ravelli, A., Sattar, N. A., Stamm, T., et al. (2022) · RMD Open · doi:10.1136/rmdopen-2022-002359 · Cited by 49
Akaishi, T., Takeshita, T., Himori, N., Takahashi, T., Misu, T., Ogawa, R., Kaneko, K., Fujimori, J., Abe, M., Ishii, T., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00932 · Cited by 49
Tur, C., Dubessy, A., Otero‐Romero, S., Amato, M. P., Derfuss, T., Pauli, F. D., Iacobaeus, E., Mycko, M. P., Abboud, H., Achiron, A., et al. (2022) · Multiple Sclerosis Journal · doi:10.1177/13524585211069068 · Cited by 50
Targeting B cells to modify MS, NMOSD, and MOGAD
Graf, J., Mareš, J., Barnett, M. H., Aktaş, O., Albrecht, P., Zamvil, S. S., & Hartung, H.-P. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000919 · Cited by 48
Longitudinal follow-up of serum biomarkers in patients with neuromyelitis optica spectrum disorder
Kim, H., Lee, E., Kim, S., Choi, L., Kim, H. J., Kim, H. W., Chung, K., Seo, D., Moon, S., Kim, K., et al. (2021) · Multiple Sclerosis Journal · doi:10.1177/13524585211024978 · Cited by 43
Schindler, P., Aktaş, O., Ringelstein, M., Wildemann, B., Jarius, S., Paul, F., & Ruprecht, K. (2022) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2023.2148657 · Cited by 43
Advances in the Treatment of Neuromyelitis Optica Spectrum Disorder
Wallach, A. I., Tremblay, M. A., & Kister, I. (2020) · Neurologic Clinics · doi:10.1016/j.ncl.2020.09.003 · Cited by 38
“An open-label randomized phase 2 trial (TANGO) included 118 patients with active NMOSD who were randomized 1:1 to either tocilizumab, 8 mg/kg, monthly IV infusions or azathioprine, 2 to 3 mg/kg, oral daily.(4) Analysis of the primary outcome of time to first relapse favored tocilizumab over azathioprine with a median…”
BackgroundMethodAdverse Events in NMOSD Therapy
Giglhuber, K., & Berthele, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084154 · Cited by 38
“, one as due to “central respiratory failure secondary to myelitis involving the high cervical spine and medulla oblongata”, the other to “severe myelitis” [41,44].”
BackgroundMethodNeuromyelitis Optica Spectrum Disorders
Costello, F. (2022) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001168 · Cited by 38
Pïcca, A., Valyraki, N. E., Birzu, C., Kramkimel, N., Hermine, O., Zahr, N., Berzero, G., & Psimaras, D. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001073 · Cited by 40
“Tocilizumab has recently demonstrated its efficacy in patients with ICI-related cerebritis(5) and other non-ICI-related CNS inflammatory conditions, such as neuromyelitis optica spectrum disorder (NMOSD).(6) Similarly, ruxolitinib was also effective in a patient with severe NMOSD.”
BackgroundYin, H., Wang, Y., Liu, M., Zhang, D., Ren, H., Mao, Z., Zhang, Y., Peng, B., Cui, L., & Xu, Y. (2023) · Annals of Neurology · doi:10.1002/ana.26623 · Cited by 36
Neuromyelitis Optica Spectrum Disorder Treatment—Current and Future Prospects
Waliszewska‐Prosół, M., Chojdak-Łukasiewicz, J., Budrewicz, S. P., & Pokryszko‐Dragan, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062801 · Cited by 35
“An openlabel, multicenter, randomized phase 2 trial (TANGO) [65] demonstrated the advantage of tocilizumab over AZA in achieving clinical endpoints (reduced relapse rate and sustained disability), with a small percentage of severe outcomes and a mild increase in transaminases as the main adverse effects [29,64,66].”
BackgroundIn‐depth peripheral CD4+ T profile correlates with myasthenic crisis
Huan, X., Luo, S., Zhong, H., Zheng, X., Song, J., Zhou, L., Lü, J., Wang, Y., Xu, Y., Xi, J., et al. (2021) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51312 · Cited by 34
Huang, W., Wang, L., Xia, J., Li, W., Wang, M., Yu, J. Y., Li, Q., Wang, B., Pan, J., Du, L., et al. (2022) · European Journal of Neurology · doi:10.1111/ene.15355 · Cited by 32
Häußler, V., Trebst, C., Engels, D., Pellkofer, H., Havla, J. B., Duchow, A. S., Schindler, P., Schwake, C., Pakeerathan, T., Fischer, K., et al. (2024) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2024-334764 · Cited by 31
“26 Although the numbers for immunotherapies other than rituximab and eculizumab were relatively small in our study, we could support this observation and validate these findings for NMOSD in our multivariate model for rituximab and eculizumab.”
Du, L., Chang, H., Xu, W., Wei, Y., Wang, Y., Yin, L., & Zhang, X. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118217 · Cited by 31
Self-citationVelasco, M., Zarco, L. A., Agudelo-Arrieta, M., Torres-Camacho, I., Garcia-Cifuentes, E. R., & Múñoz, Ó. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.102869 · Cited by 31
Solomon, J. M., Paul, F., Chien, C., Oh, J., & Rotstein, D. (2021) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864211014389 · Cited by 32
Drug Treatment of Neuromyelitis Optica Spectrum Disorders: Out with the Old, in with the New?
Held, F., Klein, A.-K., & Berthele, A. (2021) · ImmunoTargets and Therapy · doi:10.2147/itt.s287652 · Cited by 30
Li, Z., Zhang, C., Chang, T., Zhang, X., Yang, H., Gao, F., Feng, J., Liu, H., Chen, S., Wang, L., et al. (2023) · The Lancet Regional Health - Western Pacific · doi:10.1016/j.lanwpc.2023.100846 · Cited by 29
Self-citationCurrent perspectives on the diagnosis and management of acute transverse myelitis
Tisavipat, N., & Flanagan, E. P. (2023) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2023.2195095 · Cited by 27
“antibody, was compared head-to-head to azathioprine in a randomized, open-label TANGO trial [182].”
Sechi, E. (2024) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001454 · Cited by 30
Treatment and Relapse Prevention of Typical and Atypical Optic Neuritis
Saitakis, G., & Chwalisz, B. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179769 · Cited by 27
“The authors concluded that tocilizumab significantly reduced the risk of relapse compared with azathioprine in NMOSD, proposing the agent as a potentially effective and safe treatment for relapse prevention in NMOSD [107,132].”
BackgroundInfluentialKonitsioti, A., Prüß, H., Laurent, S. A., Fink, G. R., Heesen, C., & Warnke, C. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12642-4 · Cited by 28
Rimkus, C. D. M., Schoeps, V. A., de Oliveira, M. B., Godoy, L. F. D. S., Apóstolos‐Pereira, S. L., Calich, A. L., Callegaro, D., Lucato, L. T., Rovira, À., Sastre‐Garriga, J., et al. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.103146 · Cited by 25
Zhang, T., Chen, J.-S., Chen, D., Zeng, P., Zhang, H., Wang, X., Liu, Y., Huang, Z., Yuan, M., Li, Y.-L., et al. (2021) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864211054952 · Cited by 25
Self-citationChen, D., Zeng, P., Han, J., Zhang, T., Jia, D., Shi, F., & Zhang, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.660230 · Cited by 24
Self-citationHou, Y., Chen, Z., Wang, L., Deng, Y., Liu, G., Zhou, Y., Shi, H., Shi, X., & Jiang, Q. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s360743 · Cited by 24
Responsiveness to Tocilizumab in Anti-Acetylcholine Receptor-Positive Generalized Myasthenia Gravis
Jia, D., Zhang, F., Li, H., Shen, Y., Jin, Z., Shi, F., & Zhang, C. (2023) · Aging and Disease · doi:10.14336/ad.2023.0528 · Cited by 24
“Several randomized controlled trials have shown the effectiveness of tocilizumab in autoimmune diseases including rheumatoid diseases and neuromyelitis optica spectrum disorders [9, 10].”
BackgroundSelf-citationLu, Q., Luo, J., Hao, H.-J., Liu, R., Jin, H., Jin, Y., & Gao, F. (2020) · Journal of Neurology · doi:10.1007/s00415-020-10236-4 · Cited by 24
Efficacy and safety of tocilizumab in patients with refractory generalized myasthenia gravis
Ruan, Z., Tang, Y., Gao, T., Li, C., Guo, R., Sun, C., Huang, X., Li, Z., & Chang, T. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14793 · Cited by 24
Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders
Louapre, C., Maillart, É., Papeix, C., Zeidan, S., Biotti, D., Lepine, Z., Wahab, A., Zedet, M., Labauge, P. M., Tilikete, C., et al. (2020) · European Journal of Neurology · doi:10.1111/ene.14612 · Cited by 23
“Interestingly, monoclonal antibodies such as anti-IL6 receptors (satralizumab, tocilizumab)[4,5] and C5 inhibitors (eculizumab)[6], known to reduce relapse rate in NMOSD, are currently being tested in clinical trials in COVID-19-related acute respiratory distress syndrome due to their possible effect on the ‘cytokine…”
BackgroundSellner, J., Sitte, H. H., & Rommer, P. S. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.03.018 · Cited by 23
Optic neuritis: current challenges in diagnosis and management
Bénard-Séguin, É., & Costello, F. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001128 · Cited by 22
“Copyright © 2023 Wolters Kluwer H new IL-6 inhibitors specifically designed for NMOSD [45].”
BackgroundAungsumart, S., Youngkong, S., Dejthevaporn, C., Chaikledkaew, U., Thadanipon, K., Tansawet, A., Khieukhajee, J., Attia, J., McKay, G. J., & Thakkinstian, A. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1166490 · Cited by 22
Liu, Y., Zhang, H., Zhang, T., Yuan, M., Chen, D., Zeng, P., Huang, Z., Jia, D., Yang, G., Shi, F., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.703931 · Cited by 22
“Tocilizumab also decreases serum AQP4-IgG titers in patients with highly active NMOSD (15).”
BackgroundResultSelf-citationWang, H., Zhou, J., Li, Y., Wei, L., Xu, X., Zhang, J., Yang, K., Wei, S., & Zhang, W. (2021) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864211056710 · Cited by 21
Nasonov, E. L., & Feist, E. (2022) · Rheumatology Science and Practice · doi:10.47360/1995-4484-2022-505-518 · Cited by 21
Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases
Li, J., & Guo, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.966766 · Cited by 22
“This work was supported by the National Natural Science Foundation of China (Grant no. 82072079).”
BackgroundInfluentialEmerging drugs for the treatment of neuromyelitis optica
Duchow, A. S., Chien, C., Paul, F., & Bellmann–Strobl, J. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1803828 · Cited by 20
Yin, Z., Qiu, Y., Duan, A., Fang, T., Chen, Z., Wu, J., Wang, Z., & Chen, G. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11641-1 · Cited by 20
“For example, RTX and inebilizumab [12–14] target antibody-producing B cells, eculizumab [15] targets complement protein C5, and tocilizumab [16] and satralizumab [17, 18] block interleukin-6 (IL-6) signaling.”
BackgroundXie, Q., Zheng, T., Sun, M., Sun, J., & Wang, M. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102421 · Cited by 19
Satralizumab in the Treatment of Neuromyelitis Optica Spectrum Disorder
Duchow, A. S., & Bellmann–Strobl, J. (2020) · Neurodegenerative Disease Management · doi:10.2217/nmt-2020-0046 · Cited by 19
Ding, J., Cai, Y. C., Deng, Y., Jiang, X., Gao, M., Lin, Y. Z., Zhao, N., Wang, Z., Yu, H., Lv, W., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.596791 · Cited by 19
New Therapeutic Landscape in Neuromyelitis Optica
Tugizova, M. S., Vlahovic, L., Tomczak, A. J., Wetzel, N. S., & Han, M. H. (2021) · Current Treatment Options in Neurology · doi:10.1007/s11940-021-00667-3 · Cited by 19
Immuno-pathogenesis of neuromyelitis optica and emerging therapies
Chihara, N., & Yamamura, T. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00941-9 · Cited by 19
Pediatric Neuromyelitis Optica Spectrum Disorder
Poisson, K. E., Moeller, K., & Fisher, K. S. (2023) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2023.101051 · Cited by 21
Liu, C., Shi, M., Zhu, M., Chu, F., Jin, T., & Zhu, J. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102921 · Cited by 19
Siriratnam, P., Sanfilippo, P. G., van der Walt, A., Sharmin, S., Foong, Y. C., Yeh, W. Z., Zhu, C., Khoury, S. J., Csépány, T., Willekens, B. M. P., et al. (2024) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2024-334090 · Cited by 17
“37 However, it is noteworthy that each of these studies included only approximately 15–20 sero-negative NMOSD patients, and the Satralizumab trials relied on ELISA to detect AQP4-IgG, which has a sensitivity of 60%.”
Proinflammatory cytokines and their receptors as druggable targets to alleviate pathological pain
Kalpachidou, T., Riehl, L., Schöpf, C. L., Uçar, B., & Kress, M. (2022) · Pain · doi:10.1097/j.pain.0000000000002737 · Cited by 17
Kohle, F., Dalakas, M. C., & Lehmann, H. C. (2023) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864221137129 · Cited by 17
Emerging Targeted Therapies for Neuromyelitis Optica Spectrum Disorders
Valencia-Sánchez, C., & Wingerchuk, D. M. (2020) · BioDrugs · doi:10.1007/s40259-020-00460-9 · Cited by 17
Treatment of myelin oligodendrocyte glycoprotein immunoglobulin G–associated disease
Healy, S., Elhadd, K. T., Gibbons, E. L., Whittam, D., Griffiths, M. J., Jacob, A., & Huda, S. (2021) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12630 · Cited by 17
Efficacy and safety of Tocilizumab for thyroid eye disease: a systemic review and Meta-analysis
Lin, S., Ou, X., Cai, L., Wenxin, H., & Wen, J. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02595-4 · Cited by 16
“Similarly, a previous RCT in rheumatoid arthritis showed no difference between intravenous TCZ (8 mg/kg every 4 weeks) and subcutaneous TCZ (162 mg/kg weekly) [42], supporting our subgroup findings.”
Emerging Role of Targeted Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders
Holian, A., & Weinshenker, B. G. (2025) · BioDrugs · doi:10.1007/s40259-025-00729-x · Cited by 16
Wang, M., Zeng, P., Chen, D., Xue, H., Cui, Z., Zhang, H., Jia, D., & Zhang, C. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.103035 · Cited by 16
Self-citationLin, T.-Y., Chien, C., Lu, A., Paul, F., & Zimmermann, H. G. (2021) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2021.1982697 · Cited by 16
Weinhard, J., Noble, J., Jouvé, T., Malvezzi, P., & Rostaing, L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10194359 · Cited by 13
“Due to the multiple sites of action of IL-6 and a favorable safety profile in early rheumatology cohorts, tocilizumab has been studied for many other indications over the past 15 years, including refractory Takayasu disease [31], systemic lupus erythematosus [32], giant cell arteritis [33], highly relapsing neuromyeli…”
BackgroundPathogenic antibodies to AQP4: Neuromyelitis optica spectrum disorder (NMOSD)
Wright, S. K., Wassmer, E., & Vincent, A. C. (2021) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2021.183772 · Cited by 15
Demuth, S., & Collongues, N. (2024) · Revue Neurologique · doi:10.1016/j.neurol.2024.01.008 · Cited by 15
Yang, S., Zhang, C., Zhang, T.-X., Feng, B., Jia, D., Han, S., Li, T., Shen, Y., Yan, G., & Zhang, C. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11364-9 · Cited by 15
“Furthermore, the TANGO study suggested that tocilizumab provides evident clinical efficacy for patients with NMOSD regardless of their autoimmune disease status [14].”
BackgroundSelf-citationLevraut, M., Landes-Château, C., Mondot, L., Cohen, M., Bresch, S., Brglez, V., Seitz‐Polski, B., & Lebrun‐Frénay, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.864133 · Cited by 15
Gholizadeh, S., Exuzides, A., Lewis, K. E., Palmer, C. A., Waltz, M., ROSE, J. W., Jolley, A. M., Behne, J. M., Behne, M. K., Blaschke, T. F., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11529-6 · Cited by 14
“In parallel, a recent open-label study of tocilizumab in a small number of patients with NMOSD (TANGO) [30] applied the IPND criteria and reported a 26% reduction in relapse risk compared with azathioprine.”
Metadata
- Authors
- Zhang, C., Zhang, M., Qiu, W., Ma, H., Zhang, X., Zhu, Z., Yang, C.-S., Jia, D., Zhang, T.-X., Yuan, M., Feng, Y., Yang, L., Lu, W., Yu, C., Bennett, J. L., & Shi, F.-D.
- Affiliations
- Capital Medical University (CN)
- Shanxi Medical University (CN)
- Sun Yat-sen University (CN)
- Tianjin Huanhu Hospital (CN)
- Tianjin Medical University General Hospital (CN)
- Tianjin Medical University (CN)
- University of Colorado Anschutz (US)
- Corresponding author
- Shi, Fu-Dong
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 19
- Issue
- 5
- Pages
- 391-401
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC7935423
- OpenAlex
- W3019956952
- Cited by
- 287
- References
- 27
- Citations by year
- 2026: 34 · 2025: 31 · 2024: 37 · 2023: 49 · 2022: 54 · 2021: 53 · 2020: 26
- FWCI
- 29.30
- Type
- journal article
- Language
- en
- Update notices
- erratum (2025-12-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Guthy-Jackson Charitable Foundation
- AbbVie
- Roche
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- neuromyelitis optica spectrum disorder, tocilizumab, azathioprine, relapse prevention, time to first relapse, IL-6 inhibition, immunosuppressive therapy, concomitant autoimmune disease, treatment safety, Expanded Disability Status Scale, disease-modifying therapy, China
- MeSH terms
- Adult, Azathioprine, Female, Humans, Immunosuppressive Agents, Male, Middle Aged, Neuromyelitis Optica, Treatment Outcome, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
