Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma

Abstract

Background: Nonadherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management.

Research question: The goal of this study was to evaluate 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 by using a validated LC-MS/MS assay following observed intake of prednisolone in patients receiving maintenance oral prednisolone. Patterns of adherence and nonadherence 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 receiving maintenance prednisolone and a control group.

Results: In the prednisolone absorption test, 27 patients (mean age, 38.6 years; age range, 17-63 years; 83% female) were included. We identified adherence in 13 (48%), nonadherence in 13 (48%), and malabsorption in one (3.7%). The median [interquartile range] peak serum assays of the adherent group compared with the nonadherent group were: cortisol, 36 [39.5] vs 295 [153] nmol/L; and prednisolone, 1,810 [590] vs 1,730 [727] nmol/L. The spot test cohort included 111 patients (67 on maintenance prednisolone and 44 control subjects); the mean age was 42.4 years, and 79% were female. Nonadherence was detected in 40.3% of patients; comparison of the adherent vs nonadherent groups revealed median [interquartile range] levels for cortisol of 27 [48] nmol/L vs 211 [130] nmol/L and for prednisolone of 259 [622] nmol/L vs < 20 nmol/L, respectively. Adherent patients had higher mean BMI (38.4 ± 8.7 vs 32 ± 7.5 kg/m²; P = .03), lower median blood eosinophils (0.09 [0.31] vs 0.51 [0.53] × 10⁹/L; P < .001), and a trend toward reduced mean annual severe exacerbations (3.0 ± 2.6 vs 4.3 ± 2.4; P = .3) than nonadherent patients.

Interpretation: Nonadherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic by using the LC-MS/MS assay.

Keywords: adherence; adrenal suppression; asthma; corticosteroids; cortisol; prednisolone; severe.