Background: Asthma is a highly rhythmic disease with symptoms, airflow obstruction and airway inflammation peaking overnight. Chronotherapy is the treatment strategy by aligning the timing of drug administration with the body?s circadian rhythm, in an effort to improve disease outcome.

Aim: To evaluate the efficacy of chronotherapy using ICS in asthma.

Methods: Patients with moderate atopic asthma were recruited. Following 14 days of run-in period, patients were randomised sequentially to three dosing regimens (Clenil Modulite 400µg daily dose 1. once daily between 8-9am [OD_AM], 2. once daily between 3-4pm [OD_PM] and 3. in divided dose (200µg twice daily [BD]) for 28 days, with washout of 14 days in between treatment.  Spirometry and biomarkers for airway inflammation were measured; asthma Control Questionnaire (ACQ) was assessed at baseline and at end of each treatment period.

Results: Of 25 patients, 20 (mean [SD] age: 41.3 [10.4] years, 60% male) completed the study. OD_PM improved nighttime forced expiratory volume within 1 second (FEV₁) from baseline (median [IQR]: +160 [70-258]ml, p=0.002) with a greater effect on this endpoint compared to OD_AM (+160 [28-232]ml, p=0.001), and a similar effect compared to BD. OD_PM reduced nighttime blood eosinophil counts compared to OD_AM (p=0.041) and BD (p<0.001). Whilst all regimens improved ACQ and fractional exhaled nitric oxide, there was no difference between regimens. However, a trend for better asthma control was observed in OD_PM compared to OD_AM (p=0.055).

Conclusion: Chronotherapy using ICS may improve asthma outcomes. This warrants further validation and investigation of the underlying mechanisms.