A cost-effectiveness analysis of fixed-combination therapies in patients with open-angle glaucoma: a European perspective

ABSTRACT

Objective: To compare the efficacy and cost implications of the use of the intraocular pressure-lowering prosta­glandin analogues bimatoprost, travoprost, and latano­prost as fixed-combination therapies with timolol, a β-adrenergic receptor antagonist.

Methods: A decision analytic cost-effectiveness model was constructed. Since no head-to-head studies comparing the three treatment options exist, the analysis was based on an indirect comparison. Hence, the model was based on efficacy data from five randomized, controlled, clinical studies. The studies were comparable with respect to study design, time horizon, patient population and type of end point presented. The measure of effectiveness was the percentage reduction of the intraocular pressure level from baseline. The cost evaluated was the cost of medication and clinical visits to the ophthalmologist. All drug costs were market prices inclusive of value-added tax, and visit costs were priced using official physician fees. Cost-effectiveness analyses were carried out in five European countries: Spain, Italy, United Kingdom, Norway and Sweden. The time horizon for the analyses was 3 months.

Results: The analysis showed that fixed-combination bimatoprost/timolol was more effective and less costly than fixed-combination travoprost/timolol and fixed-combination latanoprost/timolol in three out of the five countries analyzed. In two countries, bimatoprost/timolol was less costly than latanoprost/timolol, and cost the same as travoprost/timolol.

Conclusions: This cost-effectiveness analysis showed that the fixed combination of bimatoprost 0.03%/timolol 0.5% administered once daily was a cost-effective treatment option for patients with primary open-angle glaucoma. This study was limited by available clinical data: without a head-to-head trial, indirect comparisons were necessary. In the United Kingdom, Sweden, Norway, Italy, and Spain, from a health service viewpoint, bimatoprost/timolol was a slightly more effective as well as less costly treatment strategy when compared to both travoprost/timolol and latanoprost/timolol.     

Ocular hypotensive efficacy of travoprost in patients unsuccessfully treated with latanoprost

SUMMARY

Objective: To evaluate the efficacy of travoprost 0.004% monotherapy in patients unsuccessfully treated with latanoprost monotherapy.

Research design and methods: Open-label, non-comparative study conducted at US academic and private practice clinics in adult patients with ocular hypertension or primary open-angle glaucoma who required a change in therapy (due to either inadequate efficacy or safety issues) as judged by the investigator. Intraocular pressure (IOP) was measured at entry and 30?days later.

Main outcome measures: Mean change in intra-ocular pressure (mm Hg).

Results: Reported here are 488 per-protocol patients from 330 centers who were using latanoprost monotherapy prior to study entry, and who received travoprost monotherapy during the study. Patients had a mean age of 69?years, were approximately two-thirds Caucasian, 60% female, predominantly brown or blue eyes, and 91% were diagnosed as having primary open-angle glaucoma. The mean days in treatment were 31.9 ± 6.4. Mean IOP at study entry was 21.2?mm Hg. Following travoprost monotherapy, this was reduced by a mean of 3.2?mm Hg to 18?mm Hg (?p < 0.0001, paired t-test). There were 21 adverse events reported in the intent-to-treat (ITT) population for an incidence of 3.5%. There were some limitations to the current study including: no washout period, no control therapy, single IOP determinations at the beginning and the end of the study; patient compliance with the initial therapy was not measured, and the study was not masked. This study reflects a real-life situation of what a clinician can expect when he changes a patient from latanoprost monotherapy to travoprost monotherapy.

Conclusion: This study showed that travoprost provided a statistically and clinically significant reduction (?p < 0.0001) in IOP of 3.2?mm Hg for patients who had not been successfully treated with latanoprost monotherapy. The results of this trial demonstrate the potential benefit of using travoprost as a replacement therapy in order to ensure adequate IOP control.     

Concomitant administration of travoprost and brinzolamide versus fixed latanoprost/timolol combined therapy: three-month comparison of efficacy and safety

SUMMARY

Purpose: To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily.

Research, design and methods: Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy.

Main outcome measures: IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit.

Results: IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1?month, 2?month and 3?month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 ± 0.9?mmHg vs 18.4 ± 1.8?mmHg, p < 0.001) at the 3?month check. The percentage of responders (IOP decrease ≥ 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment.

Conclusions: Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.     

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%*

ABSTRACT

Purpose: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan^?) compared to latanoprost 0.005% (Xalatan^?) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension.

Methods: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients’ IOP was measured throughout two consecutive 24‐h periods every 4?h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4?h throughout two 24‐h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9?mmHg and 80% power to detect a difference of 2.5?mmHg between treatments.

Results: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant (?p < 0.05) at 12, 16, 20, 24, 36, 40, and 48?h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24‐h period of the week 2 visit as well as for the 48‐h visit were statistically lower (?p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated.

Conclusion: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.     

Neuroprotective effect of latanoprost on rat retinal ganglion cells

Background To investigate the neuroprotective effect of intravitreal administration of latanoprost on retinal ganglion cell (RGC) damage induced by N-methyl-D-aspartic acid (NMDA) or optic nerve axotomy.Methods Using Sprague-Dawley rats, retinal ganglion cell damage was induced by either intravitreal administration of NMDA or optic nerve axotomy. Latanoprost at doses of 0.03, 0.3, 3, 30 and 300 pmol was administered intravitreally before NMDA injection or optic nerve axotomy. Retinal damage was evaluated by counting the number of surviving RGCs retrogradely labeled with fluorogold under the microscope.Results Seven days after the NMDA injury, the number of surviving RGCs was significantly increased at doses of more than 30 pmol atanoprost (846±178 cells/mm² P=0.0166) compared with vehicle control (556±122 cells/mm²). Ten days after the optic nerve axotomy, the number of surviving RGC was significantly increased even at a dose of 0.3 pmol (815±239 cells/mm², P=0.0359) compared with control (462±75 cells/mm²).Conclusions Intravitreal administration of latanoprost has a neuroprotective effect on rat RGC damage induced by either NMDA or optic nerve axotomy, while its pharmacological features are different.     

HPLC法测定拉坦前列素滴眼液中15S-拉坦前列素的含量

目的：建立拉坦前列素滴眼液中杂质15S-拉坦前列素的含量测定方法。方法：色谱柱为ZORBAX SB- C18(4.6 mm′250 mm,5 mm),流动相为甲醇-乙腈-水(用冰乙酸调节pH3.0)(56∶14∶30),流速为1.0 ml.min_-1,检测波长为210 nm,进样量为100 ml。结果：在选定的色谱条件下,15S-拉坦前列素杂质与主成分可以有效分离,在0.04994～0.9988 mg.mL_-1质量浓度范围内呈良好的线性关系(r=0.9993),平均回收度为99.03%(n=9)。结论：所建立的方法可以用于拉坦前列素滴眼液中15S-拉坦前列素的含量测定。     

A systematic review of the characteristics of randomised control trials featuring prostaglandins for the treatment of glaucoma*

ABSTRACT

Aim: To classify the comparative quantity and quality of the RCT evidence of pharmacological treatment for glaucoma.

Method: A systematic review of MEDLINE, EMBASE Cochrane CENTRAL and relevant conference proceedings was conducted up to March 2007. RCTs recruiting adults with primary open angle glaucoma (POAG) and/or ocular hypertension (OH) receiving any topical medication or placebo were included. RCTs containing a prostaglandin treatment arm were specifically considered.

Results: A total of 510 publications were identified. Of these, 181 studies had a prostaglandin treatment arm. The median study duration was 12 weeks (IQR 4–13) and 78% of included trials had a duration of 3 months or less. The four studies over 1 year in duration all included a latanoprost and timolol treatment arm. There was a lack of data on younger populations (median of the mean ages of included patients was 63.4 years [IQR: 61–66 years]). Caucasians constituted 79.6% of the studied population. Evidence by ethnicity as well as by co-morbidity, was scarce. The primary outcome for 92% of studies was IOP reduction; little was reported on other indicators. Most trials reported adverse events, with hyperaemia most commonly reported.

Conclusion: The RCT evidence base for glaucoma treatment is extensive. This systematic review is the first to consider the characteristics of all RCTs containing a prostaglandin arm. The majority of trials are of short duration and focus on IOP as the efficacy outcome. The limitations of this study are that only trials with a prostaglandin treatment arm are included and due to the large number of included trials only top line data were extracted.     

拉坦前列素及噻吗心安治疗开角型青光眼的疗效观察及安全性评估

目的 研究拉坦前列素及噻吗心安治疗开角型青光眼的疗效及安全性.方法 将120例开角型青光眼患者纳入研究对象,随机分为给予拉坦前列素联合噻吗心安治疗的观察组和单独给予噻吗心安治疗的对照组,检测视野缺损情况、视网膜神经纤维层厚度并观察不良反应例数.结果 （1）观察组患者的上方视野（4.9±0.8） dB、下方视野（5.1±0.9）dB、颞侧视野（7.2±1.3）dB、鼻侧视野缺损（6.9± 1.1） dB均明显低于对照组（P＜0.05）;（2）观察组患者的上方视野（92.3±13.2）μm、下方视野（90.8± 12.1） μm、颞侧视野（74.2±10.3）μm、鼻侧视野RNFL厚度（70.8±12.3）μm均明显高于对照组（P＜0.05）;（3）两组患者发生不良反应例数比较差异无统计学意义（P＞ 0.05）.结论 拉坦前列素及噻吗心安治疗开角型青光眼有助于改善视野缺损和视网膜神经纤维层厚度,且保证相当的安全性,具有积极的临床价值.     

毛果芸香碱联合拉坦前列素治疗原发性急性闭角型青光眼的疗效观察

目的探讨毛果芸香碱联合拉坦前列素治疗原发性急性闭角型青光眼的疗效及安全性。方法随机选取2014年5月—2015年1月海南医学院附属医院眼科收治的原发性急性闭角型青光眼患者92例,随机分为对照组和治疗组,每组各46例。对照组给予拉坦前列素滴眼液,1滴/次,1次/d。治疗组在对照组的基础上给药5 min后滴加硝酸毛果芸香碱滴眼液,2~3滴/次,2~4次/d。两组均连续治疗6个月。观察两组的临床疗效,同时比较两组患者治疗前后的视力、瞳孔直径、眼压、血流动力学指标舒张末期血流速度(EDV)、收缩期峰值血流速度(PSV)、血管阻力指数(RI)及不良反应。结果治疗后,对照组和治疗组的总有效率分别为82.61%、95.65%,两组比较差异有统计学意义(P0.05)。治疗1、3、6个月,两组患者的患眼视力、瞳孔直径均较同组治疗前显著改善,同组治疗前后差异具有统计学意义(P0.05);且治疗后,治疗组患者的视力、瞳孔直径改善程度明显优于同期对照组,两组比较差异具有统计学意义(P0.05)。对照组治疗3、6个月,治疗组治疗1、3、6个月的眼压与同组治疗前相比均有显著下降,且治疗组患者眼压下降情况明显优于同期对照组(P0.05);治疗1、3、6个月,治疗组患者的EDV、PSV均明显高于对照组,而RI则明显低于对照组,同组治疗前后差异有统计学意义(P0.05);且治疗组的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。对照组和治疗组的不良反应发生率分别为10.87%、0.00%,两组比较差异有统计学意义(P0.05)。结论毛果芸香碱联合拉坦前列素治疗原发性急性闭角型青光眼疗效显著,可明显改善视力,有效提高视野,降低眼压,安全性高,具有一定的临床推广应用价值。