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.

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).

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).

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.

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.

减少糖皮质激素暴露是重症哮喘新生物治疗的主要益处，但目前没有证据表明减少糖皮质激素暴露对应于相关毒性的相应减少。

使用经过验证的糖皮质激素毒性指数 (GTI) 评估美泊利单抗治疗 12 个月后糖皮质激素毒性的变化，并将毒性变化与糖皮质激素减少和患者报告结果测量 (PROM) 的变化进行比较。

在英国地区重症哮喘专科诊所，一项由 101 名连续患有严重哮喘患者组成的纵向、真实世界前瞻性队列开始使用美泊利单抗。在开始美泊利单抗 (V1) 和治疗 12 个月后 (V2) 时记录 GTI 毒性评估、累积糖皮质激素暴露和 PROM。

口服糖皮质激素暴露显着减少（V1 中位泼尼松龙每年 4280 mg（四分位距 3083-5475 mg）与V2 2450 mg 泼尼松龙每年（1243-3360 mg）相比，p<0.001）。观察到个体毒性显着改善，但与口服糖皮质激素减少无关。平均值±sdGTI 总体改善评分 (AIS) 为 –35.7±57.8，个体患者水平的毒性变化范围广泛（AIS 范围 –165 至 +130）；70%（101 人中有 71 人）的毒性降低（AIS <0）；3%（101 人中有 3 人）没有变化（AIS=0）；27%（101 人中有 27 人）总体毒性增加。62%（101 名中的 62 名）患者的 AIS 最小临床重要差异为 ≤–10，但 AIS 与糖皮质激素减少或 PROM 变化无关。

Mepolizumab 导致口服糖皮质激素显着减少，但这与口服糖皮质激素毒性的降低无关，后者在个体患者水平上差异很大。口服糖皮质激素减少不是对美泊利单抗反应的综合衡量标准。