Serum Prednisolone Levels as a Marker of Oral Corticosteroid Adherence in Severe Asthma

J. Michael Ramsahai; Emily King; Robert Niven; Gael Tavernier; Peter A. B. Wark; Jodie L. Simpson

Disclosures

BMC Pulm Med. 2020;20(228) 

In This Article

Results

There were 19 participants identified on daily OCS in the MIMOSA study. One was excluded because they had inadvertently withheld their medication in preparation for the study visit, and another was excluded because they were taking oral hydrocortisone and not prednisolone (shown in Figure 1).

The demographic information of the remaining 17 participants is summarized in Table 1. There were no significant differences in the populations between those that were adherent compared to non-adherent with respect to sex distribution, age, BMI, prednisolone dose, inhaled corticosteroid dose, exacerbation frequency, ACQ score, FEV1, cortisol levels, ex-smoker status, or markers of type 2 inflammation. There was higher self-reported adherence in the group defined as adherent based on serum prednisolone levels. (p = 0.03).

Of these 17 participants, three (17.6%) were defined as non-adherent, (Table 2) one of which self-reported adherence of 71% in the last month, while the others self-reported 100% adherence. The remaining 14 (82.4%) participants were categorised as adherent and all self-reported adherence of 100% in the last month. Of the 14 adherent participants, six (42.9%) were categorised as having eosinophilic asthma with ongoing sputum eosinophilia and active type 2 inflammation, despite treatment. Markers of type 2 inflammation were significantly different when compared with those who did not have ongoing sputum eosinophilia (blood eosinophil count (cellsx109/L) of 0.20 vs. 0.02, p = 0.003, and elevated FeNO (in parts per billion (ppb)) of 43 vs. 12, p = 0.002) (Table 3).

Serum prednisolone levels were compared to the time interval between self-reported last prednisolone dose and time of blood sample collection for serum prednisolone measurement, and there was a significant association based on the expected pharmacokinetics of exponential decay (Pearson's correlation r = − 0.72, p = 0.004, Figure 2).

Figure 2.

Serum prednisolone levels over time from last prednisolone dose demonstrating the expected exponential decay of serum prednisolone levels due to metabolism. (Pearson's correlation, r = − 0.71, p = 0.0038)

Mean serum cortisol levels were significantly lower in oral corticosteroid adherent compared with non-adherent participants (33.0 nmol/L versus 155.2 nmol/L, p = 0.005). This difference persisted at the final visit after 1 year of follow-up for the comparison of the adherent group (15.3 nmol/L), versus non-adherent (262.5 nmol/L, p = 0.016).

Of the three participants who were non-adherent at the beginning of the study, one was lost to follow-up. One participant remained non-adherent at the end of the study (Participant 1), while the other became adherent at some point during the treatment regimen (Participant 2). FeNO and blood eosinophil count improved through the study for Participant 2, and ACQ-6 remained below 1.5 for the majority of the time. While FeNO also trended down for Participant 1, conversely, ACQ-6 remained at or above 1.5 throughout the study, while blood eosinophil count trended up (Figure 3).

Figure 3.

Markers of Inflammation (FeNO and Blood Eosinophil Count) (3A) and ACQ-6 (3B) over one year in a participant defined as non-adherent at Visit 0 and 13 (Participant 1) compared to one that was non-adherent initially (at Visit 0) but became adherent by Visit 13 (Participant 2)

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