Department of Ophthalmology, Hotel Dieu, CHU Nantes, 44093, Nantes Cedex 1, France.
Department of Endocrinology Diabetes and Nutrition, L'institut du thorax, CHU Nantes, 44093, Nantes Cedex 1, France.
Graefes Arch Clin Exp Ophthalmol. 2020 Sep;258(9):2013-2021. doi: 10.1007/s00417-020-04651-6. Epub 2020 May 13.
The clinical utility of rituximab (RTX) in Graves' orbitopathy (GO) treatment remains controversial since the discrepant results from 2 prospective randomized studies (Stan M et al. J Clin Endocrinol Metab 2015; Salvi M et al. J Clin Endocrinol Metab 2015). The aim of this study was to assess in real life the characteristics and the clinical outcomes of patients with GO treated with RTX in cases of corticosteroid resistance or corticosteroid dependence.
Multicenter French retrospective study including patients with moderate-to-severe GO requiring second-line treatment with RTX. Patients were classified according to three main baseline characteristics: clinical inflammation (CAS ≥ 3), oculomotor limitation, and visual dysfunction. Patients were considered as responders if, at 24 weeks (week 24), at least 1 of these 3 parameters improved with no worsening elsewhere.
Forty patients were included (65% smokers, 38% dysthyroidism). Thirty-two patients were treated with RTX alone (one patient excluded owing to side effects): 64.5% had favorable responses at week 24 and significant reduction in baseline CAS (3.29 ± 1.6) at 12 weeks (1.93 ± 1.1; P < 0.001) and at week 24 (1.59 ± 1.1; P < 0.001); reduction in anti-TSH receptor antibodies at week 24 (P < 0.01); and significant improvement of visual acuity (P = 0.04) and ocular hypertonia (P = 0.04) at week 12, but no improvement in oculomotor dysfunction. Eight patients needed emergency treatment with concomitant RTX and orbital decompression, with favorable outcome for 5 patients. Predictive factors for a poor response to RTX were low baseline CAS, smoker, and baseline ocular hypertonia. All patients reported good tolerance except one serious side effect (a cytokine release syndrome).
The efficiency results of RTX in reducing CAS in this cohort are just between those of Stan and Salvi. This could be explained by our delay before treatment initiation, quicker than Stan but longer than Salvi. RTX appears to be effective as a second-line treatment for the inflammatory component of GO, especially if the disease is highly active and recent.
利妥昔单抗（RTX）在格雷夫斯眼病（GO）治疗中的临床应用仍存在争议，这是由于两项前瞻性随机研究的结果存在差异（Stan M 等人，J Clin Endocrinol Metab 2015；Salvi M 等人，J Clin Endocrinol Metab 2015）。本研究的目的是在现实生活中评估接受 RTX 二线治疗的 GO 患者的特征和临床结局，这些患者存在皮质激素抵抗或皮质激素依赖。
这项多中心的法国回顾性研究纳入了需要接受 RTX 二线治疗的中重度 GO 患者。根据三种主要基线特征对患者进行分类：临床炎症（CAS≥3）、眼外肌运动受限和视觉功能障碍。如果在 24 周（第 24 周）时至少有 1 项参数改善且无其他部位恶化，则患者被认为有应答。
共纳入 40 例患者（65%为吸烟者，38%存在甲状腺功能亢进）。32 例患者单独接受 RTX 治疗（1 例因副作用被排除）：64.5%的患者在第 24 周时有良好的应答，并且在第 12 周时 CAS 基线显著降低（3.29±1.6）（1.93±1.1；P＜0.001）和第 24 周时（1.59±1.1；P＜0.001）；第 24 周时抗促甲状腺素受体抗体降低（P＜0.01）；第 12 周时视力（P=0.04）和眼内压（P=0.04）显著改善，但眼外肌运动障碍无改善。8 例患者需要同时进行 RTX 和眼眶减压的紧急治疗，其中 5 例患者的结局良好。对 RTX 反应不佳的预测因素是较低的基线 CAS、吸烟者和基线眼内压升高。除 1 例严重不良反应（细胞因子释放综合征）外，所有患者均报告良好的耐受性。
RTX 在降低本队列的 CAS 方面的疗效结果介于 Stan 和 Salvi 之间。这可能是由于我们开始治疗的时间延迟所致，比 Stan 更早但比 Salvi 更长。RTX 似乎是 GO 炎症成分的有效二线治疗药物，特别是在疾病高度活跃且为近期时。
