單方暨複方青光眼藥物之降低眼壓效果與交互作用：系統性文獻回顧與網絡統合分析

Abstract

本篇系統性回顧與網絡統合分析旨在評估青光眼藥物之降眼壓效果，比較單方和複方藥物在原發性隅角開放型青光眼或高眼壓症之病患的療效。共納入224項研究，42,260名參與者，比較36種和17類青光眼藥物的治療效果。在所有納入之藥物中，前三名有效皆為複方藥，分別為travoprost/ brinzolamide, latanoprost/brimonidine, brimonidine/ timolol/ dorzolamide。而前三名有效的單方藥為bimatoprost, latanoprostene bunod, latanoprost。此外本研究欲探討新型藥物相較於原有藥物的療效，發現新型的前列腺素omidenepag isopropyl (OMDI) 效果不如已有的前列腺素衍生物(PG)，降低眼壓效果排在bimatoprost, latanoprostene bunod, latanoprost, travoprost, tafluprost之後。然而，OMDI/timolol的組合療效較好，僅略低於bimatoprost/timolol，優於latanoprost, travoprost, tafluprost和timolol的組合。在ROCK激脢抑制劑(ROCKI)中netarsudil優於ripasudil和carbonic anhydrase inhibitors（C），而和β-阻滯劑（B）和α-2腎上腺素能促進劑（A）差不多，但效果不如前列腺素衍生物。而latanoprostene bunod作為一種效果優良的單一療法，效果僅次於bimatoprost。在複方藥物療效的部分，前列腺素衍生物之複方藥物優於非前列腺素衍生物之複方藥。而非前列腺素衍生物之複方藥物與效果較優良之前列腺素衍生物單方藥差不多，例如bimatoprost、latanoprostene bunod，較排名在後之前列腺素衍生物單方藥效果好，例如tafluprost、OMDI。在所有前列腺素衍生物之複方藥中，效果排名依次為PG+C、PG+A、PG+B+A、PG+ROCKI和PG+B。PG+B+A效果反而比PG+A來得弱，以及C作為降壓效果最弱的單方藥，其和PG之結合反而是效果最強的複方藥，這些與元件網絡統合分析的互動模式發現PG和C有加乘效應，而PG和B有拮抗效應互相應證。本研究提供了現有青光眼藥物的降低眼壓效果排名，為青光眼臨床治療選用藥物提供參考，並指出藥物間可能的交互作用，為開發新的複方療法提供基礎。

This systematic review and network meta-analysis (NMA) assessed the efficacy of monotherapy versus combination therapy in treating primary open angle glaucoma or ocular hypertension. We included 224 studies involving 42,260 participants to compare the treatment efficacy of 36 kinds and 17 categories of glaucoma medications. The top combination therapies, based on P-score, were travoprost/ brinzolamide, latanoprost/brimonidine, and brimonidine/ timolol/ dorzolamide, while the leading monotherapies included bimatoprost, latanoprostene bunod, and latanoprost. The effectiveness of newer glaucoma medications was also explored. Omidenepag isopropyl (OMDI) was less effective than established prostaglandin analog (PG), placing it after bimatoprost, latanoprostene bunod, latanoprost, travoprost, and tafluprost. However, its combination with timolol showed improved efficacy and was only inferior to bimatoprost/timolol. Netarsudil outperformed ripasudil (ROCKI) and carbonic anhydrase inhibitors (C) and matched β-blockers (B) and α-2 adrenergic agonists (A), though it was less effective than prostaglandin analogs. Latanoprostene bunod, positioned as a superior monotherapy ranking just below bimatoprost. Prostaglandin combinations generally surpassed non-prostaglandin combinations. Non-prostaglandin combinations demonstrated similar efficacy to high-ranking prostaglandin monotherapies, such as bimatoprost and latanoprostene bunod, and outperformed lower-ranking prostaglandin monotherapies like tafluprost and OMDI. The hierarchy of prostaglandin-based combination therapies—categorized as PG+C, PG+A, PG+B+A, PG+ROCKI, and PG+B—mirrored the interactive component NMA model findings of a synergistic effect between PG and C, contrasted with an antagonistic effect between PG and B. This research offers a detailed efficacy ranking of the extant glaucoma medications, providing a strategic guide for clinical practice and a foundation for developing novel combination therapies.