From the Larner College of Medicine at the University of Vermont (M.K.H., D.H., S.M.G.), Burlington; Duke University School of Medicine (L.D.H.-W.), Durham, NC; University of Miami Health System (M.B., M.A.F.), FL; University of Toronto School of Medicine (C.B.), Canada; SUNY Buffalo Jacobs School of Medicine (N.J.S.), NY; UNC School of Medicine (J.F.H.), Chapel Hill, NC; Mayo Clinic (A.V., B.A.C.), Rochester, MN; Yale School of Medicine (R.N., R.B., A.K.), New Haven, CT; Medical University of South Carolina (K.R., I.-H.A.C.), Columbia; University of Florida (M.T.P., S.M.L., Gainesville; University of Kansas Medical Center (M.P.), Kansas City; and University of Virginia School of Medicine (T.M.B.), Charlottesville.
Neurology. 2017 Sep 5;89(10):1069-1077. doi: 10.1212/WNL.0000000000004341. Epub 2017 Aug 11.
To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG).
This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs.
Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls ( = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) ( 0.001 and = 0.005).
This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.
评估利妥昔单抗治疗抗肌肉特异性激酶（MuSK）重症肌无力（MG）的疗效。
这是一项多中心、盲法、前瞻性回顾性研究，比较了接受利妥昔单抗治疗的抗 MuSK 阳性 MG 患者与未接受利妥昔单抗治疗的患者。主要临床终点是重症肌无力状态和治疗强度（MGSTI），这是一种新的结局，结合了美国重症肌无力基金会（MGFA）干预后状态（PIS）和使用的其他免疫抑制剂治疗的数量和剂量。事先，MGSTI 水平≤2 用于定义良好的结局。次要结局包括改良 MGFA 最小表现或更好的 PIS、平均/中位数泼尼松剂量以及平均/中位数其他免疫抑制剂药物剂量。
在 2005 年 1 月 1 日至 2015 年 1 月 1 日期间，对 10 个神经肌肉中心的 119 名抗 MuSK MG 患者进行了评估，在一个盲法专家小组对有限的临床数据进行审查后，其中 77 名患者入选进行分析。另外 22 名患者由于随访不足而被排除在外。利妥昔单抗治疗组（n=24）和对照组（n=31）患者的基线特征相似。中位随访时间超过 3.5 年。末次随访时，利妥昔单抗治疗组 58%（14/24）的患者达到主要结局，而对照组为 16%（5/31）（=0.002）。主要结局的治疗人数需要 2.4。末次随访时，利妥昔单抗治疗组 29%的患者服用泼尼松（平均剂量 4.5mg/天），而对照组为 74%（平均剂量 13mg/天）（<0.001 和=0.005）。
这项研究提供了 IV 级证据，表明对于抗 MuSK MG 患者，利妥昔单抗增加了良好结局的可能性。
