Rituximab for the Treatment of New-onset AChR-Myasthenia Gravis

Summary

Myasthenia gravis (MG) is the most common acquired disorder of neuromuscular junction (NMJ), the most common antibody (in 85% MG patients) being the nicotinic acetylcholine receptor (AChR). Traditional medical treatments of new-onset MG include anticholinesterase inhibitors, immunomodulating therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) and immunosuppressive agents such as corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate and cyclophosphamide. Since a status of complete stable remission (CSR, defined as remission of MG without pharmacological treatment≥1 year) is difficult to achieve, the international consensus guidance for management of MG proposed "minimal manifestation (MM) or better status" with no greater than mild adverse events as a practical goal of MG treatment. Given the balance between efficacy and safety, a more aggressive strategy and approach for immune therapies are critical in early stage of new-onset MG. In clinical practice, biological agent monoclonal antibody rituximab (RTX), specifically targeting B-lymphocyte differentiation membrane antigen CD20, has been increasing in recent years for some immune-mediated neurological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), and gradually represented potential advantages in immunosuppressive therapy-refractory and new-onset AChR-MG. However, up to now, the individualized regimen, optimal dosage and clinical benefit of RTX monotherapy for early stage of new-onset AChR-MG still need to be elucidated. This study was performed to assess the long-term clinical efficacy and safety of individualized low-dose 100 mg RTX monotherapy approach in new-onset AChR-MG patients.

Timeline

Start

2022-08-01

Primary completion

2027-06-30

Completion

2027-07-31

Publications

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• Background Yilmaz V, Maillard S, Truffault F, Bolgert F, Behin A, Regnard JF, Berrih-Aknin S, Le Panse R. Regulatory B cells in myasthenia gravis are differentially affected by therapies. Ann Clin Transl Neurol. 2018 Sep 22;5(11):1408-1414. doi: 10.1002/acn3.645. eCollection 2018 Nov.
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• Background Forsthuber TG, Cimbora DM, Ratchford JN, Katz E, Stuve O. B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Ther Adv Neurol Disord. 2018 Mar 21;11:1756286418761697. doi: 10.1177/1756286418761697. eCollection 2018.
• Background Dos Santos A, Noury JB, Genestet S, Nadaj-Pakleza A, Cassereau J, Baron C, Videt D, Michel L, Pereon Y, Wiertlewski S, Magot A. Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study. Eur J Neurol. 2020 Nov;27(11):2277-2285. doi: 10.1111/ene.14391. Epub 2020 Jul 4.
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• Background Choi K, Hong YH, Ahn SH, Baek SH, Kim JS, Shin JY, Sung JJ. Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis. Ther Adv Neurol Disord. 2019 Sep 18;12:1756286419871187. doi: 10.1177/1756286419871187. eCollection 2019.
• Background Li H, Huang Z, Jia D, Xue H, Pan J, Zhang M, Shi K, Shi FD, Zhang C. Low-dose rituximab treatment for new-onset generalized myasthenia gravis. J Neuroimmunol. 2021 May 15;354:577528. doi: 10.1016/j.jneuroim.2021.577528. Epub 2021 Feb 24.
• Background Zhang C, Bu B, Yang H, Wang L, Liu W, Duan RS, Zhang M, Zeng P, Du C, Yang L, Shi FD. Immunotherapy choice and maintenance for generalized myasthenia gravis in China. CNS Neurosci Ther. 2020 Dec;26(12):1241-1254. doi: 10.1111/cns.13468. Epub 2020 Oct 26.
• Background Li T, Zhang GQ, Li Y, Dong SA, Wang N, Yi M, Qi Y, Zhai H, Yang L, Shi FD, Yang CS. Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: A meta-analysis. J Clin Neurosci. 2021 Mar;85:6-12. doi: 10.1016/j.jocn.2020.11.043. Epub 2021 Jan 2.
• Background Lu J, Zhong H, Jing S, Wang L, Xi J, Lu J, Zhou L, Zhao C. Low-dose rituximab every 6 months for the treatment of acetylcholine receptor-positive refractory generalized myasthenia gravis. Muscle Nerve. 2020 Mar;61(3):311-315. doi: 10.1002/mus.26790. Epub 2020 Jan 6.
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• Background Du Y, Li C, Hao YF, Zhao C, Yan Q, Yao D, Li L, Zhang W. Individualized regimen of low-dose rituximab monotherapy for new-onset AChR-positive generalized myasthenia gravis. J Neurol. 2022 Aug;269(8):4229-4240. doi: 10.1007/s00415-022-11048-4. Epub 2022 Mar 3.

Drugs

Indications

No indication recorded.