Determinants of response to fluticasone propionate and salmeterol/fluticasone propionate combination in the Gaining Optimal Asthma controL study.

BACKGROUND: During the Gaining Optimal Asthma controL study, 3416 patients with uncontrolled asthma were randomized to receive salmeterol/fluticasone propionate combination (SFC) or fluticasone propionate (FP) for 1 year. Approximately two thirds of patients achieved well-controlled (WC) asthma, and one third continued to have asthma that was not well controlled (NWC). OBJECTIVE: This analysis aimed to (1) identify factors influencing treatment response and (2) assess the clinical benefits of SFC and FP in patients with NWC asthma. METHODS: Logistic regression analysis was used to investigate whether covariates influenced the achievement of at least WC asthma in the study population. In patients with NWC asthma, predefined criteria were used to assess improvements in 6 clinical outcomes. RESULTS: Factors affecting the probability of having NWC asthma included smoking status (current vs never: odds ratio [OR], 2.757; 95% CI, 2.061-3.689; P < .0001; former vs never: OR, 1.274; 95% CI, 1.031-1.574; P = 0.0273), sex (women vs men: OR, 0.652; 95% CI, 0.527-0.806; P < .0001), history of inhaled corticosteroid use (no history vs history: OR, 0.546; 95% CI, 0.437-0.683; P < .0001), and treatment (FP vs SFC: OR, 1.972; 95% CI, 1.686-2.308; P < .0001). Of patients with NWC asthma, 86% to 96% showed improvements in 1 or more clinical outcomes. CONCLUSION: It is imperative for good asthma control that patients stop smoking. Patients who did not have at least WC asthma demonstrated clinical improvements in individual asthma outcomes. CLINICAL IMPLICATIONS: Although not all patients can achieve guideline-defined control, long-term treatment with SFC or FP is associated with clinical improvements in nearly all patients, regardless of smoking history or inhaled corticosteroid use.

Rate of response of individual asthma control measures varies and may overestimate asthma control: an analysis of the goal study.

BACKGROUND: Using a composite measure based on clinical outcomes, the GOAL study showed that achievement of Total Control of asthma was time dependent with the proportion of controlled patients continuing to rise through the year-long study. Taking data from this study, we compared time taken to achieve Total Control with time taken to achieve total control of each individual clinical criterion on treatment with salmeterol/fluticasone propionate (SFC) or fluticasone propionate (FP) alone. METHODS: Time to achieving total control of individual outcomes (day-time symptoms, night-time awakenings, rescue medication use, PEF > or =80% predicted every day) were analyzed by Kaplan Meier plots and compared with achievement of composite Total Control. RESULTS: Night-time awakenings responded most rapidly and daytime symptoms took longest to respond. After 12 weeks, the proportion of patients who achieved control of any individual clinical criterion was higher than the proportion who achieved control when using the composite outcome (no night-time awakenings achieved by 73% with SFC and 65% with FP; PEF > or =80% predicted every day, 55% and 45% respectively; no rescue usage 46% and 35% respectively; and no daytime symptoms, 35% and 24% respectively, compared with Total Control, 23% and 14% respectively). In every measure except night-time awakenings, more rapid responses were seen for SFC compared with FP alone. CONCLUSIONS: Speed of response of individual asthma measures varies and evaluation of control using any single measure overestimates total asthma control. Treatment should be continued until composite control is reached, rather than control of individual outcomes.

Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.