Korobelnik Jean-Francois, Kleijnen Jos, Lang Shona H, Birnie Richard, Leadley Regina M, Misso Kate, Worthy Gill, Muston Dominic, Do Diana V
Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, F-33000 Bordeaux; Service d'Ophtalmologie, CHU de Bordeaux, Bordeaux, France.
School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Limburg, the Netherlands.
BMC Ophthalmol. 2015 May 15;15:52. doi: 10.1186/s12886-015-0035-x.
This was an indirect comparison of the effectiveness of intravitreal aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if different periods, after an initial monthly dosing period) (2q8) and other diabetic macular edema (DME) therapies at doses licensed outside the USA.
A comprehensive search was undertaken to source relevant studies. Feasibility networks were prepared to identify viable comparisons of 12-month outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were assessed for clinical and statistical homogeneity. Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one 'head-to-head' study was found then a mixed treatment comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus dexamethasone 0.7 mg implants (three studies).
There was an increase in mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by 4.67 letters [95% credible interval (CrI): 2.45-6.87] in the fixed-effect MTC model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52-7.11] in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95% CI: 1.29-3.40]) in the fixed-effect model. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants.
Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons. These analyses are subject to a number of limitations which are inherent in indirect data comparisons.
本研究为间接比较，比较了在最初每月注射5次（或不同疗程时，在最初每月注射疗程后）后每8周注射2毫克玻璃体内阿柏西普（IVT - AFL）（2q8）与美国以外地区获批剂量的其他糖尿病性黄斑水肿（DME）治疗方法的疗效。
进行全面检索以获取相关研究。准备可行性网络以确定IVT - AFL 2q8与美国以外地区获批治疗方法之间12个月结局的可行比较，并对其进行临床和统计学同质性评估。使用固定效应模型和随机效应模型计算合并效应量（平均差[MD]和相对风险/风险比[RR]）。使用布彻分析进行间接比较。如果发现至少一项“头对头”研究，则使用贝叶斯方法进行混合治疗比较（MTC）。基于间接分析可进行两项12个月的比较：IVT - AFL 2q8与按需注射0.5毫克玻璃体内雷珠单抗（IVR）（10项研究）以及IVT - AFL 2q8与0.7毫克地塞米松植入物（3项研究）。
在固定效应MTC模型（10项研究）中，与按需注射0.5毫克IVR相比，IVT - AFL 2q8使平均最佳矫正视力（BCVA）提高了4.67个字母[95%可信区间（CrI）：2.45 - 6.87]；在布彻间接分析（4项研究）中提高了4.82个字母[95%置信区间（CI）：2.52 - 7.11]。与0.7毫克地塞米松植入物相比，在固定效应模型中，IVT - AFL 2q8使12个月时视力提高≥10个早期治疗糖尿病性视网膜病变研究字母的患者比例增加了一倍（RR = 2.10 [95% CI：1.29 - 3.40]）。IVT - AFL 2q8与按需注射0.5毫克IVR或0.7毫克地塞米松植入物之间在安全性结局方面无显著差异。
基于间接比较，与按需注射0.5毫克IVR和0.7毫克地塞米松植入物的研究相比，IVT - AFL 2q8的研究显示12个月时视力测量结果有所改善。这些分析存在一些间接数据比较中固有的局限性。
