Mixed treatment comparison and meta-regression of the efficacy and safety of prostaglandin analogues and comparators for primary open-angle glaucoma and ocular hypertension

Abstract

Objectives:

Primary open-angle glaucoma (POAG) is a chronic condition characterised by optic neuropathy and vision loss. Elevated intraocular pressure (IOP) can damage the optic nerve and is a risk factor for glaucoma, thus treatment usually comprises topical hypotensives. This analysis aims to address methodological issues associated with the synthesis of glaucoma clinical trial data, given variations in study methodology and IOP measurement.

Methods:

Meta-regression was used to estimate how IOP varies over time for patients receiving treatment. Relative treatment effects were assessed using a random-effects mixed treatment comparison (MTC) in order to preserve randomisation and avoid selection bias. To produce clinically meaningful outputs, these analyses were combined to obtain the mean on-treatment IOP and the proportion of patients achieving different IOP targets at different time points. A further MTC estimated the probability of hyperaemia events.

Results:

The analysis showed that after 3 months’ treatment, between 58 and 83% of patients will have a ≥20% reduction in IOP and 70–93% of patients will have an absolute IOP <20 mmHg. Latanoprost and bimatoprost were found to produce significantly lower on-treatment IOP compared with timolol (p < 0.05); the difference between latanoprost and bimatoprost was not significant. Travoprost produced a lower mean IOP compared with timolol (not significant). Latanoprost-timolol was found to produce significantly lower IOP than latanoprost alone or β-blockers. The probability of hyperaemia-type events varied between treatments from 14.8 to 63.03%. Latanoprost had significantly lower odds of hyperaemia than travoprost, bimatoprost, travoprost-timolol, or bimatoprost-timolol.

Conclusion:

This analysis suggests that latanoprost and bimatoprost produce a statistically significant reduction in IOP compared with timolol, but are associated with a higher risk of hyperaemia. Out of all the prostaglandins, latanoprost may achieve a good balance between tolerability and IOP efficacy. As with all forms of meta-analysis, the results are based on the assumption that the studies and intervention groupings are sufficiently similar to be compared.

Key words::

• Meta-analysis
• Meta-regression
• Mixed treatment comparison
• Ocular hypertension
• Open-angle glaucoma
• Prostaglandin analogues

Transparency

Declaration of funding

This research was funded by Pfizer Ltd, Walton on the Hill, Surrey, UK.

Declaration of financial/other relationships

S.K. and J.L. have disclosed that they are employees of Pfizer. M.O., H.D. and S.C. have disclosed that they have undertaken paid consultancy work on behalf of Pfizer.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgement

The authors thank Nicky Welton for her advice on the WinBUGS code and also thank the Abacus systematic review/data extraction team for their involvement in the project.