Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.
Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.
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DOI：
10.1001/jamaophthalmol.2013.195
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发表时间：
2013-06
影响因子：
8.1
通讯作者：
Dana, Reza
中科院分区：
文献类型：
--
作者：
Amparo, Francisco;Dastjerdi, Mohammad H.;Okanobo, Andre;Ferrari, Giulio;Smaga, Leila;Hamrah, Pedram;Jurkunas, Ula;Schaumberg, Debra A.;Dana, Reza
干眼病是最常见的眼科疾病之一，其免疫发病机制尚未完全阐明。这项前瞻性、双盲、随机试验的数据表明，通过局部应用IL-1拮抗剂靶向白细胞介素1（IL-1），可有效显著减少DED相关患者症状和角膜上皮病变。评价局部IL-1受体拮抗剂阿那白滞素（Kineret; Amgen Inc）治疗与睑板腺功能障碍相关的DED患者的安全性和疗效。前瞻性I/II期、随机化、双盲、溶剂对照临床试验。75例难治性DED患者。受试者随机接受局部阿那白滞素2.5%（n=30）、阿那白滞素5%（n=15）或溶剂（1%羧甲基纤维素）（n=30）治疗，每日3次，持续12周。主要结局为角膜荧光素染色（CFS）、双侧CFS完全清除、通过眼表疾病指数测量的干眼相关症状、泪膜破裂时间和睑板腺分泌质量。与载体相比，局部阿那白滞素耐受性良好，没有可归因于治疗的严重不良反应的报告。经过12周的治疗，2.5%阿那白滞素治疗的参与者的平均CFS评分降低了46（与溶剂相比P= 0.12，与基线相比P<0.001）;接受阿那白滞素治疗的参与者，5%，平均CFS评分降低17（与载体相比P=.88，与基线相比P=.33）;用载体治疗的患者的平均CFS评分降低19%（P=.11）。阿那白滞素组28例患者中有8例（29%）双侧CFS完全清除，2.5%，而溶媒组29例患者中有2例（7%）双侧CFS完全清除（P=.03）。到第12周，2.5%阿那白滞素治疗和5%阿那白滞素治疗使症状分别显着减轻30%和35%（与溶剂相比，P= 0.02和P= 0.01）;溶剂治疗导致症状减轻5%。用2.5%阿那白滞素局部治疗12周是安全的，并显著减轻了DED患者的症状和角膜上皮病变。这些数据表明，使用IL-1拮抗剂可能作为DED患者的一种新的治疗选择。
The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. Seventy-five patients with refractory DED. Participants were randomized to receive treatment with topical anakinra, 2.5% (n=30), anakinra, 5% (n=15), or vehicle (1% carboxymethylcellulose) (n=30) 3 times daily for 12 weeks. Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye–related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P=.12 compared with vehicle and P<.001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P=.88 compared with vehicle and P=.33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P=.11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2of 29 patients (7%) treated with vehicle (P=.03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P=.02 and P=.01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms. Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED.
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影响因子：
4.4
作者：
Chotikavanich S;de Paiva CS;Li de Q;Chen JJ;Bian F;Farley WJ;Pflugfelder SC
通讯作者：
Pflugfelder SC
影响因子：
4.4
作者：
Kimura, Kazuhiro;Teranishi, Shinichiro;Nishida, Teruo
通讯作者：
Nishida, Teruo
影响因子：
3.4
作者：
De Paiva, Cintia S.;Corrales, Rosa M.;Pfiugfelder, Stephen C.
通讯作者：
Pfiugfelder, Stephen C.
影响因子：
13.7
作者：
Sall, K;Stevenson, OD;Reis, BL
通讯作者：
Reis, BL
影响因子：
13.7
作者：
Barber, LD;Pflugfelder, SC;Foulks, GN
通讯作者：
Foulks, GN