Netarsudil shows lower IOP reduction but better conjunctival hyperemia profile versus prostaglandin analogues

This Bayesian network meta-analysis evaluated the efficacy and safety of netarsudil, alone or in fixed-dose combinations, compared to prostaglandin analogues (PGAs) for primary open-angle glaucoma or ocular hypertension. The study included 5,390 patients with a 3-month follow-up, focusing on mean intraocular pressure (IOP) reduction as the primary outcome and conjunctival hyperemia incidence as a key safety measure.

The primary efficacy analysis revealed a clear hierarchy for IOP reduction. Fixed-dose combinations of netarsudil were most effective, followed by bimatoprost, travoprost, latanoprost, tafluprost, and netarsudil monotherapy. This ranking indicates that while netarsudil-based therapies are effective, monotherapy may be less potent than several PGA options for lowering IOP.

Regarding safety, the incidence of conjunctival hyperemia showed a different pattern. Tafluprost had the highest incidence, followed by fixed-dose combinations, netarsudil, bimatoprost, travoprost, and latanoprost. Netarsudil demonstrated a relatively lower incidence of this common side effect compared to tafluprost and the fixed-dose combinations, suggesting a favorable tolerability profile.

The study's Bayesian approach allowed for comprehensive comparisons across multiple treatments, even with limited direct trial data. This methodology is particularly valuable in ophthalmology, where head-to-head trials are often scarce. The analysis synthesized evidence from various sources to provide a robust ranking of treatment options.

Limitations include potential bias in assessing conjunctival hyperemia, as this outcome may be reported inconsistently across studies. The analysis did not report absolute numbers, effect sizes, or confidence intervals for the hierarchies, which limits the precision of the findings. Additionally, the 3-month follow-up may not capture long-term efficacy or safety trends.

Despite these limitations, the results have significant clinical implications. Netarsudil may serve as a valuable alternative for patients intolerant to PGAs or those requiring adjunctive therapy. Its distinct efficacy and safety profile could help personalize treatment plans for glaucoma management.

In practice, clinicians should consider the trade-offs between IOP reduction and side effect profiles when selecting therapies. Netarsudil's lower hyperemia incidence may improve adherence in patients sensitive to this side effect, while its IOP-lowering efficacy, though lower than some PGAs, remains clinically meaningful.

Overall, this meta-analysis provides a nuanced view of netarsudil's role in glaucoma treatment, highlighting its potential as a well-tolerated option with a unique balance of benefits and risks.