Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years
Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years
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DOI：
10.1016/j.ophtha.2005.05.013
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发表时间：
2005-10-01
期刊：
影响因子：
13.7
通讯作者：
Foulks, GN
中科院分区：
文献类型：
--
作者：
Barber, LD;Pflugfelder, SC;Foulks, GN
目的：评价0.1%环孢素眼用乳剂对中、重度干眼病患者1~3年的疗效。设计：非随机、多中心、开放标签临床试验，延长2个眼用环孢素III期临床试验。参与者：412名患者，在之前的III期临床试验中，用0.05%或0.1%环孢素治疗6~12个月。干预：患者每天两次向双眼滴入0.1%环孢素眼用乳剂，连续3个月延长至12个月。主要观察指标：角膜染色、Schirmer试验和症状严重性评估，在前12个月延长期间，在第二次延长12个月期间进行患者调查。在6个月期间进行生物显微镜和视力(VA)检查、眼压(IOP)测量和不良反应询问。结果：平均治疗时间为19.8个月。干眼病的客观和主观指标的改善是适度的，可能是因为之前接受了环孢素治疗。大多数调查受访者表示，在之前的III期临床试验中，他们的症状在环孢素治疗的前3个月开始缓解。在研究结束时，视力下降了12.6%(93/738)，增加了5.4%(40/738)；生物显微镜检查发现的严重程度增加了3.4%(结膜水肿；26/760)、7.2%(结膜充血；55/760)或8.5%(泪膜碎片；/756)；平均眼压比基线增加了0.18毫米汞。最常见的治疗相关不良事件是灼热(10.9%的患者[45/412])、刺痛(3.9%[16/412])和结膜充血(3.4%[14/412])。未发生与治疗相关的严重不良事件。95.2%(140/147)的患者表示将继续使用环孢素治疗，97.9%(143/146)的患者会推荐其他干眼症患者使用。结论：0.1%环孢素眼用乳剂治疗慢性干眼病1~3年安全、耐受性好，且不存在全身不良反应。这一结果补充了商业上可获得的0.05%环孢素眼用乳剂的安全性记录。(C)2005年由美国眼科学会颁发。
Objective: To evaluate cyclosporine 0.1 % ophthalmic emulsion over a 1- to 3-year period in moderate to severe dry eye disease patients.Design: Nonrandomized, multicenter, open-label clinical trial extending 2 ophthalmic cyclosporine phase III clinical trials.Participants: Four hundred twelve patients previously dosed for 6 to 12 months with cyclosporine 0.05% or 0.1 % in prior phase III trials.Intervention: Patients instilled ophthalmic cyclosporine 0.1 % twice daily into both eyes for up to 3 consecutive 12-month extension periods.Main Outcome Measures: Corneal staining, Schirmer tests, and symptom severity assessments were conducted during the first 12-month extension, with a patient survey during the second 12-month extension. Biomicroscopy and visual acuity (VA) examinations, intraocular pressure (IOP) measurements, and adverse effects queries occurred at 6-month intervals.Results: Mean duration of treatment was 19.8 months. Improvements in objective and subjective measures of dry eye disease were modest, probably because of prior treatment with cyclosporine. Most survey respondents said their symptoms began to resolve in the first 3 months of cyclosporine treatment during the previous phase III clinical trials. At study exit, VA decreased in 12.6% (93/738) and increased in 5.4% (40/738) of eyes by >= 2 lines; severity of biomicroscopy findings increased in 3.4% (chemosis; 26/760), 7.2% (conjunctival hyperemia; 55/760), or 8.5% (tear film debris; 64/756) of eyes; and mean IOP increased 0.18 mmHg relative to baseline. The most common treatment-related adverse events were burning (10.9% of patients [45/412]), stinging (3.9% [16/412]), and conjunctival hyperemia (3.4% [14/412]). No serious treatment-related adverse events occurred. Most patients (95.2% [140/147]) said they would continue cyclosporine therapy; 97.9% (143/146) would recommend it to other dry eye patients.Conclusions: Therapy of chronic dry eye disease with cyclosporine 0.1 % ophthalmic emulsion for 1 to 3 years was safe, well tolerated, and not associated with systemic side effects. The results supplement the safety record of the commercially available cyclosporine 0.05% ophthalmic emulsion. (c) 2005 by the American Academy of Ophthalmology.