The cost-effectiveness of bimatoprost, latanoprost and timolol in treatment of primary open angle glaucoma in five European countries

OBJECTIVE: The objective of this cost-effectiveness analysis is to evaluate cost-effectiveness ratios of the intraocular pressure (IOP)-lowering agents bimatoprost, latanoprost and timolol in five major European countries: France, Germany, Italy, Spain and the UK. METHODS: The cost-effectiveness analysis is based on achievement of IOP targets between 13 and 18 mm Hg. Thus, the cost-effectiveness ratios express the costs of having one patient successfully achieving IOP target. The perspective of the analysis is that of the health care sector payer, including costs of medicine and costs of ophthalmologist visits. The time frame is first year of glaucoma treatment. Four treatment strategies are analysed: Timolol as first line with add-on latanoprost or bimatoprost if IOP targets are not met, and latanoprost and bimatoprost as first line with add-on timolol. RESULTS: In the UK, Spain, Italy and Germany the timolol first with add-on of bimatoprost is the least expensive treatment. This strategy dominates both strategies involving latanoprost (as add-on to timolol or as first line) in these four countries. The incremental cost-effectiveness ratio of bimatoprost first-line therapy versus timolol with add-on bimatoprost varies from each country and target (from 305 pounds sterlings to 43,720 euros per patient). In France the timolol first line and latanoprost add-on is not dominated and is the cheapest alternative. The incremental cost-effectiveness ratio of timolol with add-on bimatoprost versus add-on latanoprost lies between 71 euros and 355 euros per patient depending on target (18 and 13 mm Hg, respectively). CONCLUSION: First-line treatment of latanoprost is dominated in all countries. In four out of five countries the timolol first-line therapy with add-on latanoprost is also dominated. Based on this pharmacoeconomic analysis, the most cost-effective strategy seems to be timolol first line with add-on bimatoprost if target is not met after 3 months.     

Analytic review of bimatoprost,latanoprost and travoprost in primary open angle glaucoma

ABSTRACT

Objective: The objective of this review was to evaluate different measures of efficacy of the intraocular pressure (IOP) lowering lipid class agents bimatoprost, latanoprost and travoprost in the treatment of primary open angle glaucoma. Study arms of timolol in trials including the above mentioned lipid class drugs were also included.

Methods: MEDLINE and EMBASE were searched for randomized clinical trials including one or more of the lipid class drugs bimatoprost, latanoprost and travoprost. The study results were pooled, and the simple, weighted IOP-lowering efficacy was compared among the lipid class drugs and timolol, where data were available. Efficacy parameters were reviewed, including mean reduction of IOP and percentage of patients achieving different levels of IOP.

Results: 161 articles were identified of which 42 were included in the analysis. A total of 9295 patients participated in the included trials. Based on all studies, timolol on average had a weighted mean IOP reduction of 22.2%, while latanoprost, travoprost and bimatoprost had a weighted mean IOP reduction of 26.7%, 28.7% and 30.3%, respectively. Analysis of target achievement to various IOP levels shows that bimatoprost seems more efficacious than latanoprost. The direct comparisons (head-to-head studies) also show that bimatoprost is the most efficacious treatment, however it is not conclusive whether latanoprost or travoprost is better in reducing IOP.

Conclusions: This review shows that bimatoprost seems to be the most efficacious treatment in lowering IOP. Head-to-head studies confirm this.     

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.     

Bimatoprost: a pharmacoeconomic review of its use in open-angle glaucoma and ocular hypertension

Bimatoprost (Lumigan) is a prostamide analogue used for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. In comparative clinical trials of up to 1 year in duration, administration of 0.03% bimatoprost ophthalmic solution once daily was more effective than 0.5% timolol twice daily and at least as effective as the prostaglandin analogues 0.005% latanoprost and 0.004% travoprost once daily in terms of reducing IOP and/or achieving target IOP levels. Bimatoprost was also more effective than twice-daily administration of 0.5%/2% timolol/dorzolamide in patients refractory to topical timolol therapy. Although generally well tolerated, bimatoprost is associated with a higher incidence of conjunctival hyperaemia than latanoprost, timolol or the combination of timolol and dorzolamide. Three fully published modelled cost-effectiveness analyses of bimatoprost evaluating cost per treatment success in patients with glaucoma or ocular hypertension have been conducted in the US. The analyses incorporated results of randomised, multicentre clinical trials and used a 1-year time horizon. In the treatment algorithm used in the models, patients not achieving target IOP levels with bimatoprost or comparator required additional medical visits and adjunctive therapy. Bimatoprost was associated with lower costs per treatment success than latanoprost, timolol or timolol/dorzolamide across a range of clinically relevant target IOPs. Results were sensitive to changes in treatment success rates and/or drug acquisition costs. Along with the inherent limitations of economic models, other possible criticisms of the analyses are the use of selected IOP data, and the lack of inclusion of costs associated with conjunctival hyperaemia or other adverse effects of therapy. Various other cost-effectiveness analyses of bimatoprost are available, primarily as abstracts and/or posters. In general, most of these studies have also been favourable for bimatoprost, despite having been conducted in different countries and/or from different perspectives.In conclusion, in patients with open-angle glaucoma or ocular hypertension, bimatoprost is an effective and generally well tolerated therapeutic option, albeit with a relatively high incidence of conjunctival hyperaemia. Although results of modelled cost-effectiveness analyses should be interpreted with due consideration of the limitations of the studies, available pharmacoeconomic data generally support the use of bimatoprost as a cost-effective treatment in this patient population.     

A Markov modelled pharmacoeconomic analysis of bimatoprost 0.03% in the treatment of glaucoma as an alternative to filtration surgery in Italy

ABSTRACT

Objective: Glaucoma is generally managed by decreasing the intraocular pressure (IOP) to a level believed to prevent further damage to the optic disc and loss of visual field. This may be achieved medically or surgically. The objective of this pharmacoeconomic analysis was to investigate the 4‐year costs of bimatoprost 0.03% (Lumigan) eye drops as an alternative to filtration surgery (FS) for glaucoma patients on maximum tolerable medical therapy (MTMT).

Research design and method: A Markov model was designed using effectiveness and resource use data from a randomized clinical trial and expert statements (Delphi panel). The RCT covered 83 patients on MTMT. The model compared bimatoprost with FS. In the bimatoprost model arm patients began treatment with bimatoprost. If target IOP (–20%) was not reached using medical therapy the patient proceeded with FS. In the FS model arm, FS was performed after the first ophthalmologist visit. Unit costs were obtained from an Italian chart and tariffs review (healthcare sector perspective).

Results: The RCT showed that 74.7% of the patients delayed the need for FS by 3 months. The Markov model forecasted that 64.2% of the patients could delay the need for FS by 1 year, and forecasted 34.0% could avoid FS after 4 years. The 4‐year cost per patient in the bimatoprost and FS arms was €3438 and €4194, respectively (incremental costs of €755). The major cost drivers for the bimatoprost arm were patients who needed combination therapy or FS if the target IOP was not reached. In the FS arm, the major cost drivers were the initial surgery costs and pressure-lowering medications used as add-on therapy after FS.

Conclusions: The analysis shows that in a 4‐year perspective bimatoprost is cheaper compared to FS. In addition, the postponement of FS associated with bimatoprost may have important implications for waiting list planning.     

Cost considerations in the medical management of glaucoma in the US: estimated yearly costs and cost effectiveness of bimatoprost compared with other medications

INTRODUCTION: The aim of this study was to evaluate the cost effectiveness of glaucoma treatment with bimatoprost compared with other intraocular pressure (IOP)-lowering medications in adult patients with chronic glaucoma or ocular hypertension (IOP of between 22 mm Hg and 34 mm Hg), from a US healthcare payers' perspective. METHODS: Estimated yearly costs and cost per treatment success for 0.03% bimatoprost once daily (Lumigan) were compared with 0.5% timolol twice daily (generic), 0.005% latanoprost once daily (Xalatan) and the fixed combination of 0.5% timolol and 2.0% dorzolamide twice daily (Cosopt). The model was based on year 2003 medical resource costs (physician visits and drug acquisition costs) and treatment success rates from published clinical trials. The clinical measure utilised was the percentage of patients achieving target IOPs. RESULTS: A higher percentage of patients achieved target IOPs with bimatoprost than with each of the other medications. At most target pressures, the cost per treatment success for patients starting treatment on bimatoprost was less than that for patients started on other drugs. This was true despite that, when looking at costs alone, the estimated yearly costs for bimatoprost (averaged over both patient success and patient failures) were similar to or greater than those for the other drugs.The greatest differences in cost per treatment success were seen at target pressures < or =15 mm Hg. For example, at a target pressure of 13 mm Hg, the cost per treatment success based on the model was 9238-10,229 US dollars for bimatoprost, 23,218 US dollars for timolol, 21,943 US dollars for latanoprost and 16,034 US dollars for timolol/dorzolamide. The incremental cost of achieving additional clinical success for bimatoprost ranged from 800 US dollars to 1,700 US dollars versus generic timolol, and from 300 US dollars to 3,100 US dollars versus timolol/dorzolamide. Bimatoprost was more effective and less costly than latanoprost. CONCLUSION: In our simplified model of cost per treatment success based on responder rates at varying IOPs, the greater efficacy of bimatoprost resulted in a cost per treatment success that was generally lower for bimatoprost than for timolol, latanoprost or timolol/dorzolamide. This was most pronounced at target pressures <15 mm Hg.     

Analytic review of bimatoprost, latanoprost and travoprost in primary open angle glaucoma

OBJECTIVE: The objective of this review was to evaluate different measures of efficacy of the intraocular pressure (IOP) lowering lipid class agents bimatoprost, latanoprost and travoprost in the treatment of primary open angle glaucoma. Study arms of timolol in trials including the above mentioned lipid class drugs were also included. METHODS: MEDLINE and EMBASE were searched for randomized clinical trials including one or more of the lipid class drugs bimatoprost, latanoprost and travoprost. The study results were pooled, and the simple, weighted IOP-lowering efficacy was compared among the lipid class drugs and timolol, where data were available. Efficacy parameters were reviewed, including mean reduction of IOP and percentage of patients achieving different levels of IOP. RESULTS: 161 articles were identified of which 42 were included in the analysis. A total of 9295 patients participated in the included trials. Based on all studies, timolol on average had a weighted mean IOP reduction of 22.2%, while latanoprost, travoprost and bimatoprost had a weighted mean IOP reduction of 26.7%, 28.7% and 30.3%, respectively. Analysis of target achievement to various IOP levels shows that bimatoprost seems more efficacious than latanoprost. The direct comparisons (head-to-head studies) also show that bimatoprost is the most efficacious treatment, however it is not conclusive whether latanoprost or travoprost is better in reducing IOP. CONCLUSIONS: This review shows that bimatoprost seems to be the most efficacious treatment in lowering IOP. Head-to-head studies confirm this.     

A meta-analysis of topical prostaglandin analogues intra-ocular pressure lowering in glaucoma therapy

ABSTRACT

Objective: To compare the ef?cacy of latanoprost, bimato­prost and travoprost for lowering IOP in patients with glaucoma.

Research design and methods: In order to carry out this meta-analysis, randomized trials (2001–2004) were identi?ed on Medline and EMBASE using the following key words: glaucoma, ocular hypertension (OHT), random­ization, trial, latanoprost, bimatoprost and travoprost. The studies had to compare at least two prostaglandin analogues as mono-therapy. Cross-over experimental designs were excluded. The main outcome measure was IOP at ?nal visit. Statistical analyses included random effects, pooled estimates of treatment effects, tests for publication bias, and random-effects models to obtain adjusted treatment effects on ?nal IOP after lowering for baseline IOP, and duration of follow-up. Random effects Poisson regression models were used to estimate the adjusted effects of treatments on response rates (IOP < 18?mmHg).

Results: Nine studies were used in the analysis. Patient mean age varied from 56.7 to 68.8 years and baseline IOP ranged from 22.3 to 26.5?mmHg. Three hundred and seventy-eight patients were treated with bimatoprost, 385 with travoprost and 555 with latanoprost. Patients treated with travoprost and bimatoprost had lower IOP levels at the end of follow-up (–0.98?mmHg [95% CI: –2.08; 0.13; p = 0.08] and –1.04?mmHg [95% CI: –2.11;0.04; p = 0.06], respectively) than those treated with latanoprost. The combined effect of newer prostaglandin analogues (bimatoprost/travoprost) was an adjusted decrease of 1.00?mmHg [95% CI: –1.91;–0.10], p = 0.03], or a 17% higher adjusted response rate (Incidence Rate Ratio 1.17, 95% CI, 1.00–1.35, p = 0.04), compared to latanoprost.

Conclusion: Travoprost and bimatoprost may have greater ef?cacy in lowering IOP for patients with OHT or glaucoma.     

Efficacy,tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter,open-label observational study*

ABSTRACT

Objective: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort^?) among German patients.

Methods: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n?=?606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4–6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded.

Results: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a β-blocker. Mean treated baseline IOP (±SD) for all patients was 20.7?±?3.5?mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6?±?2.7?mmHg (p?<?0.001 vs. baseline) after 4–6 weeks and to 16.1?±?2.6?mmHg (p?<?0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a β-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18?mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.     

Travoprost versus latanoprost combinations in glaucoma:economic evaluation based on visual field deficit progression

ABSTRACT

Objective: Changes in intraocular pressure (IOP) are known to be related to visual field deficit progression, although multiple models of this relationship exist. In addition, visual functioning is known to affect medical costs. The objective of this study was to project visual field deficitprogression and subsequent costs based on clinical trial data.

Research design and methods: Using data from a randomized, 12‐month, double-masked study, we compared the use of a fixed combination of travoprost 0.004%/timolol 0.5% (T/T) versus a fixed combination of latanoprost 0.005%/timolol 0.5% (L/T) on visual field deficit progression and associated costs. We applied published algorithms linking IOP to visual field changes to calculate the likelihood of visual field deterioration by treatment group. Differences in medical care costs were estimated using guideline-recommended practice patterns, Medicare hospital costs, and published estimates of differences in hospitalization by visual functioning.

Main outcome measures: Increase in visual field deficit progression rates, increase in annual hospital days per subject, and increase in annual hospital, outpatient, and total costs per subject.

Results: Predicted visual field deficit progression for T/T patients was less than that for L/T patients (not statistically significant). Projected annual medical care costs were $43 lower for T/T vs. L/T patients.

Conclusions: By applying published algorithms linking IOP to visual field changes, this study projected long-term visual field deficit and associated costs. Use of a fixed travoprost/timolol solution may lead to less long-term visual field deficit progression and lower annual medical care costs than a fixed latanoprost/timolol solution.

Discussion: The use of clinical trial data may limit the applicability of these findings. However, this analysis of direct medical costs only is likely a conservative estimate of the costs associated with visual field deficits.     

Three-month,randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACT

Objective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension.

Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n?=?101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n?=?79).

Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov.

Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire.

Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p?=?0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p?=?0.213). Patients on brimonidine–timolol reported less burning (p?<?0.001), stinging (p?<?0.001), and unusual taste (p?<?0.001) than patients on dorzolamide–timolol.

Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.     

An update on bimatoprost in glaucoma therapy

Bimatoprost, a prostamide, effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. In clinical trials, bimatoprost has demonstrated superiority to the beta-adrenergic antagonist timolol and has consistently provided approximately 1-2 mmHg greater mean IOP lowering than the prostaglandin latanoprost. Bimatoprost is more effective than either timolol or latanoprost in allowing patients to reach the low target pressures that best protect the visual field. Patients on bimatoprost therapy achieve low pressures throughout the day and night. Moreover, 1-year trials have shown that the efficacy of bimatoprost is sustained with long-term use. The most common side effects have been conjunctival hyperaemia, graded as trace or mild, and eyelash growth. No safety concerns have arisen in postmarketing surveillance. Bimatoprost appears to be a valuable new agent for glaucoma therapy.     

Bimatoprost: a member of a new class of agents,the prostamides,for glaucoma management

Bimatoprost, a synthetic analogue of endogenous prostamides, is in development as a topical ocular hypotensive agent for the treatment of glaucoma and ocular hypertension. Prostamides are a newly discovered class of compounds that have been shown to have potent ocular hypotensive activity in the laboratory. Bimatoprost mimics the endogenous prostamides by lowering intraocular pressure (IOP). Bimatoprost provides outstanding control of IOP throughout the day, and a high percentage of patients receiving bimatoprost achieve the low target pressures important for clinical success. In controlled clinical trials, bimatoprost 0.03% given once daily has displayed efficacy superior to timolol 0.5% given twice daily, the current standard for therapy. Analysis of pooled six month data from two large Phase III trials demonstrated that mean IOP was consistently 2 - 3 mmHg lower with bimatoprost q.d. than with timolol b.i.d. Bimatoprost 0.03% q.d. has also been shown to provide significantly better diurnal IOP control than latanoprost 0.005% q.d., probably the most efficacious topical medication currently available. Patients receiving bimatoprost q.d. were more likely than timolol or latanoprost patients to achieve low target pressures. In all clinical evaluations, bimatoprost q.d. has been demonstrated to be safe and well-tolerated. Bimatoprost will likely be available for clinical use in 2001 and it has great potential to be superior to all other medications in IOP-lowering efficacy. It is anticipated that bimatoprost will have an important role in therapy for glaucoma and ocular hypertension.     

Estimated first-year costs of prostaglandin analogs with/without adjunctive therapy for glaucoma management:a United States perspective

ABSTRACT

Objective: To evaluate costs associated with prostaglandin analogs among newly-diagnosed glaucoma patients in a managed-care population.

Research design and methods: A cost minimization model compared annual costs for patients initiating therapy with one of the three prostaglandin analogs (bimatoprost, latanoprost, travoprost). The study cohort was identified from pharmacy claims and eligibility files of patients who met study inclusion criteria. Annual costs were estimated for patients initiating therapy with each prostaglandin based on treatment patterns and medication use over the year. Costs for outpatient physician visits and medications were estimated from standard sources.

Results: A total of 4444 patients met study criteria: 674 received travoprost, 729 received bimatoprost, and 3041 received latanoprost. More than 80% stayed on monotherapy for 1 year (82.9% of travoprost patients, 82.8% of bimatoprost patients, and 80.5% of latanoprost patients). Of those who required adjunctive therapy, the average number of days until starting adjunctive therapy was 130 days for travoprost patients, 94 days for bimatoprost patients, and 104 days for latanoprost patients. Average annual costs were $1198, $1290, and $1217 for patients treated with travoprost, bimatoprost, and latanoprost, respectively.

Conclusions: The use of adjunctive therapy in glaucoma is an important driver of glaucoma management costs. This study demonstrates that the longer duration of monotherapy and the likelihood to use single rather than combination adjunctive agents contribute to lower annual costs among patients starting on travoprost compared with the other available prostaglandin analogs. Study limitations include the lack of clinical indicators in the study database; further, results may not be generalizable to patients who discontinue prostaglandin analogs or to the population of patients with glaucoma as a whole. Future studies with clinical and compliance indicators would further identify distinctions among treatment regimens.     

Bimatoprost: a member of a new class of agents, the prostamides, for glaucoma management

Bimatoprost, a synthetic analogue of endogenous prostamides, is in development as a topical ocular hypotensive agent for the treatment of glaucoma and ocular hypertension. Prostamides are a newly discovered class of compounds that have been shown to have potent ocular hypotensive activity in the laboratory. Bimatoprost mimics the endogenous prostamides by lowering intraocular pressure (IOP). Bimatoprost provides outstanding control of IOP throughout the day, and a high percentage of patients receiving bimatoprost achieve the low target pressures important for clinical success. In controlled clinical trials, bimatoprost 0.03% given once daily has displayed efficacy superior to timolol 0.5% given twice daily, the current standard for therapy. Analysis of pooled six month data from two large Phase III trials demonstrated that mean IOP was consistently 2 - 3 mmHg lower with bimatoprost q.d. than with timolol b.i.d. Bimatoprost 0.03% q.d. has also been shown to provide significantly better diurnal IOP control than latanoprost 0.005% q.d., probably the most efficacious topical medication currently available. Patients receiving bimatoprost q.d. were more likely than timolol or latanoprost patients to achieve low target pressures. In all clinical evaluations, bimatoprost q.d. has been demonstrated to be safe and well-tolerated. Bimatoprost will likely be available for clinical use in 2001 and it has great potential to be superior to all other medications in IOP-lowering efficacy. It is anticipated that bimatoprost will have an important role in therapy for glaucoma and ocular hypertension.     

An update on bimatoprost in glaucoma therapy

Bimatoprost, a prostamide, effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. In clinical trials, bimatoprost has demonstrated superiority to the β-adrenergic antagonist timolol and has consistently provided ～ 1 – 2 mmHg greater mean IOP lowering than the prostaglandin latanoprost. Bimatoprost is more effective than either timolol or latanoprost in allowing patients to reach the low target pressures that best protect the visual field. Patients on bimatoprost therapy achieve low pressures throughout the day and night. Moreover, 1-year trials have shown that the efficacy of bimatoprost is sustained with long-term use. The most common side effects have been conjunctival hyperaemia, graded as trace or mild, and eyelash growth. No safety concerns have arisen in postmarketing surveillance. Bimatoprost appears to be a valuable new agent for glaucoma therapy.     

A comparison of the safety and intraocular pressure lowering of bimatoprost/timolol fixed combination versus latanoprost/timolol fixed combination in patients with open-angle glaucoma*

ABSTRACT

Purpose: To compare the efficacy and tolerability of a once daily evening dose of the latanoprost/timolol fixed combination (LTFC) with that of a once-daily evening dose of the bimatoprost/timolol fixed combination (BTFC) in patients with open-angle glaucoma with elevated intrao­cular pressure (IOP) insufficiently responsive to mono­therapy with prostaglandin analogues/prostamides.

Design: Prospective, randomized, evaluator masked, single-center study.

Participants: 36 patients with a diagnosis of open-angle glaucoma, with or without pseudoexfoliation, and inadequate control of IOP, insufficiently responsive to monotherapy with prostaglandin analogues/prostamides.

Main outcome measure: The primary end-points were the change in IOP at 9:00?am from baseline to week 4, and the difference between treatment groups in the mean diurnal IOP reduction from baseline to week 4.

Results: BTFC provided significantly greater mean diurnal IOP reduction [mean (standard deviation)] 2.8 (0.9)?mmHg, compared with LTFC 2.1 (0.6)?mmHg, p = 0.0214. Both treatments significantly reduced the IOP from baseline at each IOP time-point measured, p < 0.0001, and for the mean diurnal IOP; p = 0.0049 for the LTFC, and p < 0.0001 for the BTFC. There were no significant differences in average hyperemia scores among groups, 1.25 (0.5) vs. 1.62 (0.69), p = 0.3835, for the LTFC and the BTFC, respectively.

Conclusions: The results of this study showed a significantly higher IOP-lowering effect of a once-daily evening dose of the BTFC compared to that of a once-daily evening administration of the LTFC.     

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.     

Topical bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension

Bimatoprost, a synthetic prostamide analogue, is a new ocular hypotensive agent indicated for the second-line treatment of open-angle glaucoma and ocular hypertension. The drug is formulated as a 0.03% ophthalmic solution. Bimatoprost lowers intraocular pressure (IOP) by increasing aqueous humour outflow. When applied topically once daily in patients with ocular hypertension or glaucoma, bimatoprost 0.03% significantly reduced IOP. Mean IOP was reduced by approximately 7.5 to 9.2mm Hg 12 hours after drug administration in randomised clinical trials. The reduction in IOP was maintained throughout the 24-hour dosage interval. Once-daily treatment with bimatoprost 0.03% was found to be significantly more effective than timolol 0.5% (administered twice daily as an ophthalmic solution or once daily as a gel-forming solution) in randomised comparative trials in patients with ocular hypertension and glaucoma. Furthermore, after 1 to 6 months' treatment, the percentage of patients reaching a target IOP of < or =17mm Hg was significantly greater in the bimatoprost-treated groups than in those receiving timolol. Bimatoprost 0.03% ophthalmic solution was found to be at least as effective as topical latanoprost 0.005% administered once daily in two clinical trials. Reductions in IOP 16 and 20 hours postdose were greater in patients treated with bimatoprost, indicating superior control of IOP at timepoints throughout the dosage interval. In patients refractory to beta-blocker therapy, treatment with bimatoprost 0.03% produced greater reductions in diurnal IOP measurements than combination therapy with topical dorzolamide 2%/timolol 0.5%; approximately twice as many bimatoprost 0.03% recipients achieved an IOP of < or =16mm Hg. The most commonly reported adverse effect during clinical trials of once-daily bimatoprost 0.03% was conjunctival hyperaemia which occurred in 42 to 46% of patients treated. However, most cases were mild and only 1 to 4% of patients withdrew from treatment as a result. Overall withdrawal rates as a result of adverse events during clinical trials ranged from 2.6 to 7%. Bimatoprost has been reported to cause changes in the pigmentation of the periorbital skin, eyelashes and iris, and increase eyelash growth. The long-term consequences of these effects are unknown. Cardiopulmonary adverse effects, which have been associated with the use of beta-blockers such as timolol, were not reported in clinical trials of bimatoprost. Thus, in clinical trials of up to 1-year duration, bimatoprost 0.03% has been found to be effective in significantly lowering IOP and is generally well tolerated. It provides an alternative treatment option for patients in whom beta-blockers are contraindicated. Furthermore, bimatoprost provides an effective second-line treatment option in patients who do not achieve target IOP with other topical ocular hypotensive agents, or who experience unacceptable adverse effects. Wider clinical use of this drug will establish the place of bimatoprost in the treatment of open-angle glaucoma and ocular hypertension.