Leukotriene antagonists as first-line or add-on asthma-controller therapy.

BACKGROUND: Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

Cost effectiveness of leukotriene receptor antagonists versus inhaled corticosteroids for initial asthma controller therapy: a pragmatic trial.

BACKGROUND: Information is lacking on the relative effectiveness and cost effectiveness--in a primary-care setting--of leukotriene receptor antagonists (LTRAs) as an alternative to inhaled corticosteroids (ICS) for initial asthma controller therapy. OBJECTIVE: To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy. METHODS: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma and symptoms requiring regular anti-inflammatory therapy (n = 326) were randomly assigned to LTRAs (n = 162) or ICS (n = 164). The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Questionnaire, per point improvement in the Asthma Control Questionnaire and per QALY gained from the UK NHS and societal perspectives. RESULTS: Over 2 years, resource use was similar between the two treatment groups, but the cost to society per patient was significantly higher for the LTRA group, at pounds sterling 711 versus pounds sterling 433 for the ICS group (adjusted difference pounds sterling 204; 95% CI 74, 308) [year 2005 values]. Cost differences were driven primarily by differences in prescription drug costs, particularly study drug costs. There was a nonsignificant (imputed, adjusted) difference between treatment groups, favouring ICS, in QALYs gained at 2 years of -0.073 (95% CI -0.143, 0.010). Therapy with LTRAs was, on average, a dominated strategy, and, at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained, the probability of LTRAs being cost effective compared with ICS was approximately 3% from both societal and NHS perspectives. CONCLUSIONS: There is a very low probability of LTRAs being cost effective in the UK, at 2005 values, compared with ICS for initial asthma controller therapy. TRIAL REGISTRATION: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.

Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial.

BACKGROUND: Information is lacking on the relative effectiveness and cost effectiveness--in a real-life primary-care setting--of leukotriene receptor antagonists (LTRAs) and long-acting beta2 adrenergic receptor agonists (beta2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS). OBJECTIVE: To estimate the cost effectiveness of LTRAs compared with long-acting beta2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS. METHODS: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma insufficiently controlled with ICS (n = 361) were randomly assigned to add-on LTRAs (n = 176) or long-acting beta2 agonists (n = 185). The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), per point improvement in the Asthma Control Questionnaire (ACQ) and per QALY gained from perspectives of the UK NHS and society. RESULTS: Over 2 years, the societal cost per patient receiving LTRAs was pounds sterling 1157 versus pounds sterling 952 for long-acting beta2 agonists, a (significant, adjusted) increase of pounds sterling 214 (95% CI 2, 411) [year 2005 values]. Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs (95% CI -0.077, 0.103). The incremental cost per QALY gained from the societal (NHS) perspective was pounds sterling 22,589 (pounds sterling 11,919). Uncertainty around this point estimate suggested that, given a maximum willingness to pay of pounds sterling 30,000 per QALY gained, the probability that LTRAs are a cost-effective alternative to long-acting beta2 agonists as add-on therapy was approximately 52% from both societal and NHS perspectives. CONCLUSIONS: On balance, these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting beta2 agonists as add-on therapy to ICS for asthma. However, there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs. TRIAL REGISTRATION: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.