Department of Ophthalmology, Maastricht University Medical Centre, P. Debyelaan 25, 6229, HX, Maastricht, The Netherlands.
Graefes Arch Clin Exp Ophthalmol. 2012 May;250(5):713-20. doi: 10.1007/s00417-011-1844-0. Epub 2011 Nov 27.
Adalimumab, a humanized monoclonal antibody targeted against TNF-α, has proved to be successful in the treatment of uveitis. Another anti-TNF-α agent, i.e., infliximab, has been reported of benefit in the treatment of refractory sarcoidosis. The aim of this prospective case series was to evaluate the effect of adalimumab on intraocular inflammatory signs and other relevant clinical manifestations (lung function, serological inflammatory parameters, and fatigue) of sarcoidosis.
Sarcoidosis patients with refractory posterior uveitis (n = 26, 17 females, 41 eyes in total) were systematically followed for 12 months after initiation of adalimumab 40 mg sc once a week. Inclusion criteria were non-responsiveness to prednisone and methotrexate (MTX) or intolerance to these drugs. Adjunctive therapy with prednisone and MTX was tapered during treatment with adalimumab. Localization and improvement, stabilization or deterioration of intraocular inflammatory signs was scored. Pulmonary function- and laboratory testing were performed and Fatigue Assessment Scale was completed. Results at baseline, 6 months, and 12 months were compared.
Choroidal involvement resolved in 10/15 patients, five had partial improvement; vasculitis resolved in 1/1 patient; papillitis resolved in 7/8 patients, one had partial response; macular edema resolved in 5/8 patients, three had partial response; vitreous cleared completely in 5/5 patients. Overall outcome regarding intraocular inflammatory signs showed improvement in 22 patients (85%) and stabilization in four patients (15%). At 12 months, no recurrences were reported in those successfully treated. Laboratory parameters of inflammatory activity (C-reactive protein; serum angiotensin-converting enzyme and soluble interleukin-2 Receptor) improved (p < 0.01). Moreover, fatigue improved in 14/21 (67%) of the patients suffering from fatigue and the diffusion capacity for carbon monoxide (DLCO) improved in 7/8 (88%) of patients with a decreased DLCO (p < 0.01). The dosage of both prednisone and MTX could be tapered down significantly (p < 0.01 and p < 0.05, respectively).
Adalimumab appeared successful in sarcoidosis patients with refractory chronic non-infectious uveitis showing improvement in intraocular inflammatory signs as well as in other relevant clinical indicators of disease activity. Future randomized studies are needed to determine the optimal dosage, dose interval and duration of therapy in refractory multisystemic sarcoidosis.
阿达木单抗是一种针对 TNF-α 的人源化单克隆抗体，已被证明可成功治疗葡萄膜炎。另一种抗 TNF-α 药物，即英夫利昔单抗，已被报道可有效治疗难治性结节病。本前瞻性病例系列研究旨在评估阿达木单抗对结节病的眼内炎症体征和其他相关临床表现（肺功能、血清炎症参数和疲劳）的影响。
26 例（17 名女性，共 41 只眼）难治性后葡萄膜炎结节病患者在开始每周皮下注射阿达木单抗 40mg 后系统随访 12 个月。纳入标准为对泼尼松和甲氨蝶呤（MTX）无反应或不能耐受这些药物。在使用阿达木单抗治疗期间，逐渐减少泼尼松和 MTX 的辅助治疗。对眼内炎症体征的定位和改善、稳定或恶化进行评分。进行肺功能和实验室检查，并完成疲劳评估量表。比较基线、6 个月和 12 个月的结果。
15 例患者中 10 例脉络膜受累缓解，5 例部分缓解；1 例血管炎缓解；8 例视神经炎中 7 例缓解，1 例部分缓解；8 例黄斑水肿中 5 例缓解，3 例部分缓解；5 例玻璃体完全清亮。22 例（85%）患者的眼内炎症体征总体改善，4 例（15%）患者稳定。在成功治疗的患者中，12 个月时无复发报告。炎症活动的实验室参数（C 反应蛋白；血清血管紧张素转换酶和可溶性白细胞介素-2 受体）改善（p<0.01）。此外，14/21 例（67%）患有疲劳的患者疲劳得到改善，7/8 例（88%）一氧化碳弥散量（DLCO）降低的患者 DLCO 得到改善（p<0.01）。泼尼松和 MTX 的剂量均显著减少（p<0.01 和 p<0.05）。
阿达木单抗治疗难治性慢性非感染性葡萄膜炎结节病患者有效，可改善眼内炎症体征及其他疾病活动相关的临床指标。需要进一步的随机研究来确定难治性多系统结节病的最佳剂量、剂量间隔和治疗持续时间。
