Cost-effectiveness of formoterol and salbutamol as asthma reliever medication in Sweden and in Spain. A cost-effectiveness study comparing the as-needed use of formoterol (Oxis) and terbutaline (Bricanyl) in patients with moderate to severe asthma. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.
This study aimed to evaluate the cost-effectiveness of formoterol (Oxis) Turbuhaler 4.5 microg and salbutamol 200 microg as reliever medications in Sweden and Spain. The study used data on effectiveness (exacerbations and symptom-free days) and resource utilisation from an open, 6-month, parallel-group, multicentre randomised trial with 18,124 asthma patients in 24 countries. Country-specific unit costs for Sweden and for Spain were used to transform resource utilisation data into costs. Total healthcare costs were not significantly different between formoterol and salbutamol dry powder inhalers in Sweden, whereas in Spain, the healthcare costs were 20% higher for formoterol vs. salbutamol pressurised metered dose inhalers. Total healthcare costs increased with disease severity, defined according to the Global Initiative for Asthma guidelines. Compared with salbutamol, formoterol produced statistically significant improvements in effectiveness, less reliever and maintenance medication usage, reduced healthcare resource utilisation, with no increase or a limited increase in healthcare cost. This study evaluated the economic and health-related consequences of the as-needed use of a long-acting beta2-agonist with fast onset (formoterol, Oxis Turbuhaler 4.5 microg) versus a short-acting beta2-agonist (terbutaline, Bricanyl Turbuhaler 0.5 mg) in patients with moderate to severe asthma. A multi-national (Sweden, Norway, The Netherlands and Greece), multi-centre (35 centres), randomized, double-blind clinical trial was conducted using 362 patients on inhaled steroids during a 12-week period. The effectiveness results were pooled and the total costs included estimates for beta2-agonists, inhaled steroids, oral steroids, physician visits and sick-leave. The 182 patients in the formoterol group had 14,404 days of exposure and 29 severe exacerbations, and the 180 patients in the terbutaline group had 13,655 days of exposure and 48 severe exacerbations. The terbutaline group had 62% more severe exacerbations than the formoterol group (P=0.039), based on exposure time. Per patient, the calculated total costs were SEK 3386 for the formoterol group and SEK 3709 for the terbutaline group over the 12-week period. The conclusion is that the use of Oxis Turbuhaler instead of Bricanyl Turbuhaler for as-needed treatment is a more effective treatment generating cost savings from a societal perspective. The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy.
                We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more.
                Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated.
                Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.
In adults, formoterol was similar to short-acting beta2-agonists when used as a reliever, and showed a reduction in the number of exacerbations requiring a course of oral corticosteroids. Clinicians should weigh the relatively modest benefits of formoterol as-needed against the benefits of single inhaler therapy and the potential danger of long-term use of long-acting beta2-agonists in some patients. We did not find evidence to recommend changes to guidelines that suggest that long-acting beta2-agonists should be given only to patients already taking inhaled corticosteroids.
There was insufficient information reported from children in the included trials to come to any conclusion on the safety or efficacy of formoterol as relief medication for children with asthma.