Department of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Ophthalmology. 2012 Jun;119(6):1223-30. doi: 10.1016/j.ophtha.2011.12.030. Epub 2012 Mar 3.
To compare tacrolimus monotherapy with tacrolimus and prednisone therapy for the maintenance of disease remission in subjects with noninfectious posterior segment intraocular inflammation (PSII).
Randomized, controlled, phase 2b, open-label, dual-center noninferiority trial.
Fifty-eight patients with sight-threatening PSII.
Patients requiring a second-line systemic immunosuppressive agent to control their PSII were treated with therapeutic doses of oral tacrolimus. Those subjects who subsequently were able to taper their prednisone dose to 10 mg daily without disease reactivation were assigned randomly either to stop prednisone or to continue 7.5 to 10 mg prednisone daily for 9 months.
Change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) and rate of patient withdrawal resulting from treatment inefficacy or intolerance.
Thirty-five patients successfully tapered their prednisone to 10 mg daily. Of these, 16 were allocated randomly to receive tacrolimus monotherapy and 19 to continue taking prednisone and tacrolimus dual therapy. The difference in the mean change in VA for monotherapy compared with the dual therapy group was less than 1 logMAR letter (logMAR, -0.008; 95% confidence interval, -0.108 to 0.092; P = 0.870). The proportion of patients who tolerated treatment and maintained disease remission for 9 months after randomization also was similar in both groups (monotherapy, 62.5%; dual therapy, 68.4%; P = 0.694). All monotherapy treatment failures were the result of disease reactivation, whereas 50% of dual-therapy failures were the result of drug intolerance.
This study provides preliminary evidence that corticosteroids can be withdrawn in tacrolimus-treated patients who are able to achieve control of PSII with 10 mg prednisone daily, and any advantage of dual therapy in the prevention of disease reactivation was offset by its greater treatment intolerance. These findings support the further evaluation of corticosteroid-free treatment in future phase 3 trials (International Standard Randomised Controlled Trial Number Register identification, ISRCTN46576063).
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
比较他克莫司单药治疗与他克莫司联合泼尼松治疗对非感染性后部眼内段炎症（PSII）患者维持疾病缓解的效果。
随机、对照、2b 期、开放标签、双中心非劣效性试验。
58 例视力威胁性 PSII 患者。
需要二线全身免疫抑制剂来控制 PSII 的患者接受治疗剂量的口服他克莫司治疗。那些随后能够将泼尼松剂量逐渐减少至 10mg/日而无疾病复发的患者，随机分为停止泼尼松组或继续每日服用 7.5-10mg 泼尼松 9 个月组。
最小分辨角对数（logMAR）视力（VA）的对数变化和因治疗无效或不耐受而导致的患者停药率。
35 例患者成功将泼尼松逐渐减少至 10mg/日。其中，16 例随机分配接受他克莫司单药治疗，19 例继续接受泼尼松和他克莫司联合治疗。单药治疗与联合治疗组 VA 平均变化的差异小于 1 logMAR 字母（logMAR，-0.008；95%置信区间，-0.108 至 0.092；P=0.870）。两组患者在随机分组后 9 个月内耐受治疗并维持疾病缓解的比例也相似（单药治疗组为 62.5%，联合治疗组为 68.4%；P=0.694）。所有单药治疗失败均因疾病复发所致，而联合治疗组有 50%的失败是由于药物不耐受。
本研究初步证实，对于泼尼松每日 10mg 即可控制 PSII 的他克莫司治疗患者，可以停用皮质激素，且预防疾病复发方面联合治疗的任何优势均因治疗不耐受而抵消。这些发现支持在未来的 3 期试验中进一步评估无皮质激素治疗（国际标准随机对照试验注册号登记，ISRCTN46576063）。
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