Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: A cluster-randomized trial in primary care

Background: Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (FENO), allow further tailoring of treatment. Objective: We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or FENO-driven controlled asthma (FCa). Methods: In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score < 1.50); (2) aiming at Ca (ACQ score < 0.75); and (3) aiming at FCa (ACQ score < 0.75 and FENO value < 25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate. Results: Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P <.02). There were no differences in quality of life (P >=.36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P <=.04). The FCa strategy had the highest probability of cost-effectiveness at a willingness to pay of $50,000/quality-adjusted life year (86%; PCa, 2%; Ca, 12%). There were no differences in severe exacerbation rate. Conclusion: A symptom-plus FENO-driven strategy reduces asthma medication use while sustaining asthma control and quality of life and is the preferred strategy for adult asthmatic patients in primary care.