Glucocorticoid toxicity reduction with Mepolizumab using the glucocorticoid toxicity index

P Jane McDowell, John H Stone, Yuqing Zhang, Kirsty Honeyford, Louise Dunn, R Jayne Logan, Lorcan P A McGarvey, Claire A Butler, Liam G Heaney

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Abstract

Background: Reduction in glucocorticoid exposure is the primary benefit of new biologic treatments in severe asthma, but there is currently no evidence that reduction in glucocorticoid exposure corresponds to a proportionate reduction in associated toxicity.

Objectives: To use the validated Glucocorticoid Toxicity Index (GTI) to assess change in glucocorticoid toxicity after 12 months treatment with mepolizumab, and compare toxicity change to glucocorticoid reduction and change in patient-reported outcome measures (PROMs).

Methods A longitudinal, real-world prospective cohort of 101 consecutive patients with severe asthma commenced on mepolizumab in a specialist UK regional severe asthma clinic. GTI toxicity assessment, cumulative glucocorticoid exposure and PROMs were recorded on commencing mepolizumab (V1), and after 12 months treatment (V2).

Results: There was significant reduction in oral glucocorticoid exposure (V1 median 4280 mg prednisolone per year (interquartile range 3083–5475 mg) versus V2 2450 mg prednisolone per year (1243–3360 mg), p<0.001). Substantial improvements in individual toxicities were observed, but did not correlate with oral glucocorticoid reduction. Mean±sd GTI aggregate improvement score (AIS) was −35.7±57.8 with a wide range in toxicity change at individual patient level (AIS range −165 to +130); 70% (71 out of 101) had a reduction in toxicity (AIS <0); 3% (three out of 101) had no change (AIS=0); and 27% (27 out of 101) an increase in overall toxicity. 62% (62 out of 101) of patients met the AIS minimally clinically important difference of ≤−10, but AIS did not correlate with glucocorticoid reduction or change in PROMs.

Conclusion: Mepolizumab resulted in substantial oral glucocorticoid reduction, but this did not correlate with reduction in oral glucocorticoid toxicity, which varies widely at the individual patient level. Oral glucocorticoid reduction is not a comprehensive measure of response to mepolizumab.
Original languageEnglish
JournalEuropean Respiratory Journal
Volume59
Issue number1
Early online date01 Jul 2021
DOIs
Publication statusPublished - 20 Jan 2022

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