Prostanoids in scleroderma microangiopathy: clinical and pharmacoeconomic comparison between two intravenous regimens.

Objectives: Intravenous iloprost (ILO) has widely demonstrated its effectiveness and safety in systemic sclerosis (SSc) patients. Unfortunately, there is no clear consent about dosage, duration, frequency, and infusion modality. The aim of this study was to compare two different therapeutic schemes in the same cohort of consecutive SSc subjects, evaluating differences in terms of effectiveness [digital ulcer (DU) outcome], safety, and direct healthcare costs.Method: This was a retrospective observational study of 47 patients classified with SSc treated with intravenous ILO for severe Raynaud's phenomenon and/or DUs. Two regimens were compared: a continuous inpatient scheme and a daily outpatient scheme. Demographics and clinical data, concomitant therapies, adverse events, and data on resource use and costs were collected.Results: The number of DUs rose slightly with the switch from the continuous to the daily scheme (0.61 ± 1.2 vs 1.1 ± 1.7). Moreover, in the daily scheme there was an increase in the number of therapeutic cycles (2.4 ± 0.7 vs 4.71 ± 1.4, p < 0.001) and an increase in patients treated with other vasoactive drugs. There was a reduction in ILO tolerability and more than half of the patients suspended the treatment. Five patients required hospitalization for severe and refractory DUs in the daily scheme. Moreover, the costs of the two treatments were comparable [median 7174 (range 2748-18 524) EUR vs 6284 (3232-22 706) EUR, p = 0.712].Conclusion: Treatment with a daily scheme of ILO is characterized by worse tolerability and a higher dropout rate compared to a low-flow regimen, with similar costs. We suggest that a low-flow continuous therapeutic scheme is preferable in SSc patients.

[Comparative pharmacoeconomic analysis of prostanoids for peripheral arterial occlusive].

Peripheral arteries occlusive disease (PAOD) is a prevalent illness that needs improved pharmacological management, especially for patients not eligible for surgical revascularization. Prostanoids (alprostadil or iloprost) were shown to be effective in PAOD and critical limb ischemia (CLI) but are rather costly. The results of our pharmacoeconomic study (cost estimation based on randomized control trial results) showed that iloprost does not increase cost of treatment when only direct medical costs are taken into account. If indirect costs are included into the analysis iloprost saves up to 27 thousand rubles per patient. Clinical efficacy is still high. Thus iloprost is a better alternative than alprostadil for CLI.

Cost effectiveness of prostacyclins in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is considered an orphan disease. Prostacyclins are the keystone for PAH treatment. Choosing between the three available prostacyclin therapies could be complicated because there are no comparison studies, so the final decision must be driven by factors such as efficacy, administration route, safety profile and economic aspects. OBJECTIVE: This study provides a cost-effectiveness and cost-utility comparison of initiating prostacyclin therapy with three different treatment alternatives (inhaled iloprost [ILO], intravenous epoprostenol [EPO] and subcutaneous treprostinil [TRE]) for patients with PAH. The goal of this work is to help physicians with their therapeutic decision-making. METHODS: A Markov model was built to simulate a patient cohort with class III PAH according to the classification of the New York Heart Association (NYHA). Four health states corresponding with the NYHA classes plus death were allowed for patients in the model. Changing the treatment was possible when patients worsened from functional class III to IV. The time horizon was 3 years, allowing patients to transition between health states on a 12-week cycle basis. The study perspective was that of the National Health System (NHS) [only direct medical costs were included]. Unitary costs were obtained from the Drug Catalogue and e-Salud Database in 2009 and are given in euros (€). Data on health resources and treatment pathways were informed by a four-member expert panel. Efficacy was obtained from pivotal clinical trials of ILO, EPO and TRE, the latter used in Spain as a foreign medication. Utilities for each health state were obtained from the literature. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). Costs and effects were discounted at a 3% rate. To check for the robustness of the results, sensitivity analyses were performed. RESULTS: At the end of the 3 years, in the base case of the deterministic analysis, initiating prostacyclin therapy with iloprost was the less costly strategy (€132,840), followed by treprostinil (€359,869) and epoprostenol (€429,775). Epoprostenol has shown the best efficacy results with 2.73 LYG and 1.78 QALY, followed by iloprost (2.69 LYG and 1.74 QALY) and treprostinil (2.69 LYG and 1.73 QALY). Incremental cost-effectiveness ratios (ICER) and cost-utility ratios (ICUR) of epoprostenol versus iloprost and treprostinil were much above the €30,000 per LYG or QALY threshold commonly used in Spain. Iloprost was dominant compared with treprostinil. In the probabilistic analysis, epoprostenol, when compared with iloprost, was a dominant strategy in 15% of the simulations, but it was not a cost-effective option in 83% of the cases. When compared with treprostinil, epoprostenol was dominant in 43% of the simulations. Iloprost was dominant compared with treprostinil in 45% of the cases and it was a cost-effective alternative in 39% of the simulations. CONCLUSIONS: Initiating prostacyclin treatment with iloprost in patients with PAH, functional class III of the NYHA, is the less costly alternative for the NHS in Spain, with a good efficacy profile when compared with the other alternatives.

[Pharmacoeconomics aspects of therapy for obliterating diseases of lower-limb peripheral arteries].

The study was aimed at assessing feasibility of treatment of patients suffering from critical ischaemia of lower extremities with iloprost as compared to the basic therapy by means of pharmacoeconomic analysis. The findings of clinical studies and meta-analyses demonstrated that therapy with iloprost results in a pronounced clinical effect as compared with the basic therapy: significantly (p<0.005) decreasing the number of amputations above the knee joint (23% versus 39%) and more frequently decreasing the size of trophic ulcers (in 49% of cases versus 26%). This provides maintenance of the ability to work in part of patients and a decrease in the frequency of hospitalization, which in its turn results in decreased costs of treatment and indirect expenses.. The results of the carried out study show that with due regard for only direct costs economy from treatment with iloprost would amount to 1,544,556 Roubles per 100 patients. With additionally taking into account of indirect costs economy from using iloprost as compared with basic therapy increases to 25,689,11 Roubles per 100 patients.

Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.

OBJECTIVE(S): To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications. DATA SOURCES: Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from dossiers submitted to NICE by the manufacturers of the technologies. REVIEW METHODS: The systematic clinical and economic reviews were conducted according to accepted procedures. Model-based economic evaluations of the cost-effectiveness of the technologies from the perspective of the UK NHS and personal social services were carried out. RESULTS: In total, 20 randomised controlled trials (RCTs) were included in this assessment, mostly of 12-18 weeks duration and comparing one of the technologies added to supportive treatment with supportive treatment alone. Four published economic evaluations were identified. None produced results generalisable to the NHS. There was no consensus in the industry submissions on the most appropriate model structure for the technology assessment. Improvement in 6-minute walk distance (6MWD) was seen with intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with mixed functional class (FC) (mainly III and IV, licensed indication) compared with supportive care (58 metres; 95% CI 6-110). For bosentan compared with supportive care, the pooled result for improvement in 6MWD for FCIII patients with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40 (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care. The corresponding values for inhaled iloprost (FCIII PPH patients; licensed indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed indication) and sildenafil (FCIII patients with mixed PAH; licensed indication) were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64) and [Commercial-in-confidence information has been removed] respectively. The incremental cost-effectiveness ratios (ICERs) for the technologies plus supportive care compared with supportive care alone, determined by independent economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for FCIII and 343,000 pounds/QALY for FCIV patients for epoprostenol, 101,000 pounds/QALY for iloprost, 27,000 pounds/QALY for bosentan and 25,000 pounds/QALY for sitaxentan. For the most part sildenafil plus supportive care was more effective and less costly than supportive care alone and therefore dominated supportive care. In the case of epoprostenol the ICERs were sensitive to the price of epoprostenol and for bosentan and sitaxentan the ICERs were sensitive to running the model over a shorter time horizon and with a lower cost of epoprostenol. Two RCTs directly compared the technologies against each other with no significant differences observed between the technologies. Combinations of technologies were investigated in four RCTs, with some showing conflicting results. CONCLUSION(S): All five technologies when added to supportive treatment and used at licensed dose(s) were more effective than supportive treatment alone in RCTs that included patients of mixed FC and types of PAH. Current evidence does not allow adequate comparisons between the technologies nor for the use of combinations of the technologies. Independent economic evaluation suggests that bosentan, sitaxentan and sildenafil may be cost-effective by standard thresholds and that iloprost and epoprostenol may not. If confirmed, the use of the most cost-effective treatment would result in a reduction in costs for the NHS. Long-term, double-blind RCTs of sufficient sample size that directly compare bosentan, sitaxentan and sildenafil, and evaluate outcomes including survival, quality of life, maintenance on treatment and impact on the use of resources for NHS and personal social services are needed.

Critical leg ischaemia in New Zealand: economic cost of amputation versus intravenous iloprost.

The purpose of this study was to establish the incidence of surgical amputation for critical leg ischaemia in New Zealand, and estimate the hospital, prostheses and indirect costs of this intervention. The cost of amputations was then compared with the cost of treating such patients with iloprost. The study was retrospective. Individual patient records relating to 1991 for both public and private hospitals were analysed. Unit costs relevant to 1991 were applied to the volume data of patients and procedures to derive total costs. Costs were estimated on an incremental basis taking a societal perspective. Conservative estimates were obtained for hospital costs, prostheses and for production loss (loss of output or productivity). Total cost was $NZ15.9 million (hospital and prosthesis cost $NZ13.1 million, production loss $NZ2.8 million). The total quantified cost per amputation was $NZ23 038 (hospital and prosthesis cost $NZ19 020, production loss $NZ4017). 32% of patients requiring amputations were in the working age group. The theoretical avoidance of amputation by treatment with iloprost resulted in net savings of hospital and prosthetic costs of between $NZ6660 and $NZ8720 per patient. Amputation for critical leg ischaemia is costly and has a high mortality, but for iloprost treatment to be cost effective in a New Zealand hospital setting, patients must be targeted and a success rate of at least 55% achieved in avoidance of amputation and reduction of pain while at rest.