LAUSR

BACKGROUND Non-adherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management. RESEARCH QUESTION to study the utility of liquid chromatography and tandem mass spectrometry (LC-MS/MS) in determining the adherence status to oral prednisolone in severe asthma. STUDY DESIGN AND METHODS timeline serum levels of prednisolone, cortisol and metabolites were measured using a validated LC-MS/MS assay following observed intake of prednisolone in patients on maintenance oral prednisolone. Patterns of adherence and non-adherence were determined from analysis of peak blood levels. The performance of a spot test for adherence (detectable prednisolone and suppressed cortisol) was assessed in a second cohort of patients on maintenance prednisolone and a control group. RESULTS In the prednisolone absorption test 27 patients [mean age 38.6 years (17-63), 24 (83%) females] were included. We identified adherence in 13 (48%), non-adherence in 13 (48%), and malabsorption in 1(3.7%). The median (IQR) peak serum assays (nmol/L) of the adherent compared to the non-adherent groups were; cortisol 36(39.5) vs 295(153), prednisolone 1810 (590) vs 1730(727). The spot test cohort included 111 patients [67 on maintenance prednisolone and 44 control, the mean age was 42.4 years and 79% were females. Non-adherence was detected in 40.3% of patients and comparison of the adherent versus non-adherent groups showed; cortisol 27(48) vs 211(130) and prednisolone 259 (622) vs <20 respectively. The adherent patients had higher mean BMI (38.4±8.7 vs 32±7.5kg/m2, p= 0.03), lower median blood eosinophils (90 (310) vs 510 (530) cells/μl, p< 0.001) and a trend towards reduced mean annual severe exacerbations (3.0±2.6 vs 4.3±2.4, p=0.3) than the non-adherent patients. INTERPRETATION non-adherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic using the LC-MS/MS assay.