Efficacy and tolerability of prostaglandin–timolol fixed combinations: an updated systematic review and meta-analysis

Abstract

Background:

Prostaglandin–timolol fixed combinations (PG–timolol FCs) are now widely used to reduce intraocular pressure in patients with glaucoma. The efficacy and tolerability of these drugs are worthy of further exploration. An updated systematic review and meta-analysis was performed to assess the clinical efficacy and tolerability of the three PG–timolol FCs.

Methods:

Pertinent randomized, controlled trials were identified through systematic searches of PubMed, Embase, the Cochrane central register of controlled trials and the Chinese Biomedicine Database. The main efficacy measures were the weighted mean differences (WMDs) for the reduction from baseline to end of treatment in IOP at 9 am, 12 pm and 4 pm and diurnal curve. The main tolerability measures were the odds ratios (ORs) for the incidence of conjunctival hyperemia.

Results:

Nine studies involving 991 patients were included in the meta-analysis. Latanoprost–timolol FC (LTFC) and travoprost–timolol FC (TTFC) were not significantly different in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm. Bimatoprost–timolol FC (BTFC) provided significantly greater efficacy in lowering IOP at the three measurement time points and over the mean diurnal curve than LTFC (diurnal curve: WMD = 0.88 mmHg [95% CI, 0.42 to 1.33]; 9 am: WMD = 1.27 mmHg [0.68 to 1.86]; 12 pm: WMD = 1.16 mmHg [0.85 to 1.46]; 4 pm: WMD = 0.61 mmHg [0.51 to 0.70]) and TTFC (diurnal curve: WMD = 1.94 mmHg [0.19 to 3.68]; 9 am: WMD = 0.68 mmHg [0.15 to 1.21]; 12 pm: WMD = 0.90 mmHg [0.41 to 1.39]; 4 pm: WMD = 1.06 mmHg [0.61 to 1.51]). The incidence of hyperemia was significantly higher with BTFC than LTFC (pooled ORs: 1.85 [1.09 to 3.13]). The incidence of hyperemia was not significantly higher with TTFC than LTFC (pooled ORs: 2.52 [0.85 to 7.46]), and was not significantly higher with BTFC than TTFC (pooled OR: 1.65 [0.48 to 5.70]).

Conclusions:

BTFC provided significantly greater efficacy in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm than LTFC and TTFC. LTFC was as effective as TTFC in lowering IOP at the four measurement time points and BTFC caused conjunctival hyperemia in more patients than LTFC. Further clinical trials are needed because of the limited number of studies.

Keywords: :

• Fixed combination
• Glaucoma
• Intraocular pressure
• Meta-analysis
• Prostaglandin
• timolol

Transparency

Declaration of funding

This work was supported by the Shanghai Rising-Star Program (Grant No. 12QA1404600), Shanghai Municipal Natural Science Foundation (Grant No. 10ZR1439300), and National Natural Science Foundation of China (Grant No. 81000374 and 81170874). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Declaration of financial/other relationships

H.L., H.W., Y.Z., J.-W.C. and R.-L.W. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Notes

*Xalacom is a registered trade name of Pfizer, New York, NY, USA

†DuoTrav is a registered trade name of Alcon Laboratories Inc., Fort Worth, TX, USA

‡Ganfort is a registered trade name of Allergan, Irvine, CA, USA