Department of Neurology, Academic Teaching Hospital Wels-Grieskirchen, Grieskirchner Str. 42, 4600, Wels, Austria.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
J Neurol. 2019 Mar;266(3):699-706. doi: 10.1007/s00415-019-09191-6. Epub 2019 Jan 16.
Most patients with myasthenia gravis (MG) need long-term immunosuppressive therapy. However, conventional agents may have intolerable side effects, take too long or fail to achieve disease control. Rituximab (RTX) has emerged as an off-label treatment for refractory MG, but data on its use are still sparse.
We conducted a retrospective nationwide study contacting all Austrian neurologists to provide anonymized data of all adult MG patients treated with RTX and minimum follow-up of 3 months. The Myasthenia Gravis Foundation of America Postintervention Status scale was used to assess outcomes.
34 (60.7%) of a total of 56 patients were women. Median (IQR) age at diagnosis of MG and start of RTX were 41.5 (24.3; 65.8) and 47.5 (33; 71) years, respectively. Antibodies (ab) against acetylcholine receptor (AchR) and muscle-specific tyrosine kinase (MuSK) were present in 69.6% and 25% of patients, respectively (seronegative: 5.4%). Before RTX, 47 (83.9%) patients had had plasma exchange, immune adsorption or immunoglobulins. Three months after RTX, 14 of 53 (26.4%) patients were in remission. At last follow-up after a median of 20 (10; 53) months, remission was present in 42.9% of patients and another 25% had minimal manifestations. Remission was more frequent in patients with MuSK ab vs. those with AchR ab (71.4% vs. 35.9%, p = 0.022). RTX was safe. The presence of MuSK ab independently predicted remission after RTX.
In this retrospective study on RTX for MG, the largest to date, RTX appeared safe, efficacious and fast acting. Benefit from RTX was greatest in MuSK ab + MG.
大多数重症肌无力（MG）患者需要长期免疫抑制治疗。然而，常规药物可能具有不可耐受的副作用、起效时间过长或无法控制疾病。利妥昔单抗（RTX）已被作为难治性 MG 的一种超适应证治疗药物，但关于其应用的数据仍较少。
我们进行了一项回顾性全国性研究，联系所有奥地利神经科医生，提供所有接受 RTX 治疗且随访时间至少 3 个月的成年 MG 患者的匿名数据。采用美国重症肌无力基金会干预后状态量表评估结局。
总共 56 例患者中，有 34 例（60.7%）为女性。MG 诊断和 RTX 开始时的中位（IQR）年龄分别为 41.5（24.3；65.8）岁和 47.5（33；71）岁。分别有 69.6%和 25%的患者存在乙酰胆碱受体（AchR）抗体和肌肉特异性酪氨酸激酶（MuSK）抗体（血清阴性：5.4%）。在 RTX 治疗前，47 例（83.9%）患者接受过血浆置换、免疫吸附或免疫球蛋白治疗。53 例患者中有 14 例（26.4%）在 RTX 治疗 3 个月后缓解。中位随访 20 个月（10；53）后，42.9%的患者仍缓解，另有 25%的患者症状轻微。MuSK 抗体阳性患者的缓解率高于 AchR 抗体阳性患者（71.4% vs. 35.9%，p=0.022）。RTX 是安全的。MuSK 抗体的存在独立预测 RTX 后的缓解。
在这项迄今为止最大的关于 RTX 治疗 MG 的回顾性研究中，RTX 似乎安全、有效且起效迅速。MuSK 抗体阳性的 MG 患者从 RTX 中获益最大。
