Papa Vincenzo, Galeone Carlotta, De Francesco Maria, Bodicoat Danielle H, Alves Rita, Spaepen Erik, Dart John K G, Arteaga Carlos
Medical Affairs, SIFI, Aci Sant'Antonio (Catania), Italy
University of Milan-Bicocca Faculty of Statistical Science, Milano, Italy.
BMJ Open Ophthalmol. 2025 Jul 13;10(1):e002082. doi: 10.1136/bmjophth-2024-002082.
BACKGROUND/AIMS: keratitis is a rare, severe corneal infection. Until the recent approval of polihexanide (PHMB) 0.08% by the European Medicines Agency, there were no licensed medical therapies and current treatments relied on off-label or compounded products. The purpose of this study is to estimate the relative efficacy of PHMB 0.08% compared with current treatments.
A patient-level indirect treatment comparison (ITC) compared data from a pivotal trial of PHMB 0.08% and a retrospective real-world study of current treatments: (1) any anti-amoebic treatment (AAT), (2) PHMB 0.02% plus a diamidine (propamidine or hexamidine) 0.1% and (3) chlorhexidine (CXL) 0.02% alone or in combination with a diamidine. The primary outcome was the clinical resolution rate (CRR) without surgery within 12 months. ITCs were implemented using propensity scoring analysis with overlap weighting and adjustment for covariates (age, sex, disease stage, treatment delay, prior use of corticosteroid or antiviral).
The CRR was 84.8% for PHMB 0.08% (n=66), 43.6% for any AAT (n=227), 55.0% for PHMB 0.02% plus a diamidine (n=111) and 40.0% for CXL 0.02% with or without a diamidine (n=35). In the unweighted analysis, the absolute difference (95% CI) in favour of PHMB 0.08% was 41.2% (28.8%, 51.2%; p<0.001) compared with any AAT, 29.9% (14.5%, 42.1%; p<0.001) compared with PHMB 0.02% plus a diamidine and 44.8% (23.9%, 62.3%; p<0.001) compared with CXL 0.02% with or without a diamidine. Similar results were observed in the weighted analyses.
These results suggest that PHMB 0.08% when delivered with the recommended protocol is significantly more effective than currently used treatments in achieving clinical resolution without surgery. The study limitations include differences in recruitment periods, diagnostic criteria and drug delivery methodology, as well as limitations of the ITC adjustment measures which can lead to residual confounding.
背景/目的：角膜炎是一种罕见的严重角膜感染。在欧洲药品管理局最近批准0.08%的聚六亚甲基双胍（PHMB）之前，没有获得许可的药物治疗方法，目前的治疗依赖于标签外使用或复方产品。本研究的目的是评估0.08%的PHMB与当前治疗方法相比的相对疗效。
一项患者水平的间接治疗比较（ITC）对比了0.08%的PHMB的关键试验数据和当前治疗方法的回顾性真实世界研究数据：（1）任何抗阿米巴治疗（AAT），（2）0.02%的PHMB加0.1%的双脒（丙脒或己脒），以及（3）单独使用或与双脒联合使用的0.02%的洗必泰（CXL）。主要结局是12个月内无需手术的临床缓解率（CRR）。ITC采用倾向评分分析，进行重叠加权并对协变量（年龄、性别、疾病阶段、治疗延迟、先前使用皮质类固醇或抗病毒药物情况）进行调整。
0.08%的PHMB组的CRR为84.8%（n = 66），任何AAT组为43.6%（n = 227），0.02%的PHMB加双脒组为55.0%（n = 111），0.02%的CXL单独或与双脒联合使用组为40.0%（n = 35）。在未加权分析中，与任何AAT相比，支持0.08%的PHMB的绝对差异（95%CI）为41.2%（28.8%，51.2%；p < 0.001），与0.02%的PHMB加双脒相比为29.9%（14.5%，42.1%；p < 0.001），与0.02%的CXL单独或与双脒联合使用相比为44.8%（23.9%，62.3%；p < 0.001）。在加权分析中观察到类似结果。
这些结果表明，按照推荐方案使用时，0.08%的PHMB在实现无需手术的临床缓解方面明显比目前使用的治疗方法更有效。研究局限性包括招募时期、诊断标准和药物给药方法的差异，以及ITC调整措施的局限性，这些可能导致残余混杂。
