纵向评估生物制剂对重度哮喘患者糖皮质激素毒性的降低作用
2025/01/06
摘要
背景：与口服皮质类固醇（OCS）相关的毒性已被广泛研究。针对重度哮喘（severe asthma，SA）的靶向生物制剂可显著降低OCS使用量，具有降低OCS累积毒性的潜力。糖皮质激素毒性指数（Glucocorticoid Toxicity Index，GTI）可系统评估OCS相关毒性；GTI总改善分数（Aggregate Improvement Score，AIS）是总毒性变化的双向测量指标，其最小临床重要差异值（MCID）为-10分。
目的：通过对接受生物制剂治疗的重度哮喘患者进行纵向评估，分析OCS相关毒性的变化轨迹和毒性改善的预测因素。
方法：89例重度患者在基线时、生物制剂治疗1年和3年后进行GTI评估。
结果：在3年中，日均泼尼松龙剂量持续下降[第1年6.9mg/天（4.0，9.4）vs第3年0.8mg/天（0.0，3.7），p<0.001]，OCS相关毒性持续下降[第3年AIS：-36分（-94，19），61%（54/89）的患者达到AIS MCID]。第1年和第3年的毒性变化结局呈显著正相关（p<0.001)。近一半（49%）的患者第1年和第3年末的AIS达到MCID，但29%的患者在这两个时间点的AIS均没有达到MCID。第1年毒性变化结果对3年后毒性变化的预测性为79%。毒性降低程度与OCS剂量减少不成比例，且未发现能够预测毒性降低的基线临床特征。
结论：接受生物制剂治疗3年后，61%的重度哮喘患者实现了临床显著的毒性改善。该队列1年后的毒性结局与纵向结局相关，这表明对部分患者来说，除了减少OCS，还需要额外的干预措施来降低OCS毒性发生率。
Longitudinal assessment of glucocorticoid toxicity reduction in patients with severe asthma treated with biologic therapies.
P Jane McDowell, PhD, John Busby, PhD, John H. Stone, MD, Claire A. Butler, PhD, Liam G. Heaney, MD
The Journal of Allergy and Clinical Immunology: In Practice, In Press Corrected Proof, Published online: October 28, 2024. doi: 10.1016/j.jaip.2024.10.024. PMID: 39477016
Abstract
Background: Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI aggregate improvement score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤ -10.
Objective: Longitudinal assessment of SA patients treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement.
Methods: 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy.
Results: At 3 years, daily prednisolone use continued to decrease (6.9 mg/day (4.0,9.4) year-1 v 0.8 mg/day (0.0,3.7) year-3, p<0.001), OCS-related toxicity continued to decline (AIS at 3yrs -36 (-94, 19), and 61% (54/89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at year-1 and year-3 (rho 0.65, p<0.001). Nearly half (49%) met the AIS MCID at both year-1 and 3, but 29% of the cohort did not meet the AIS MCID at either timepoint. Toxicity change at year-1 was predictive of toxicity change at year-3 for 79%. Toxicity reduction was not proportional to OCS reduction, there were no pre-biologics characteristics that predicted toxicity reduction.
Conclusions: After 3 years of biologic treatment, 61% of SA patients had clinically significant toxicity improvement. Individual toxicity outcomes at year-1 are associated with longitudinal outcomes suggesting that for some, additional interventions are needed alongside OCS-reduction to decrease morbidity.
背景：与口服皮质类固醇（OCS）相关的毒性已被广泛研究。针对重度哮喘（severe asthma，SA）的靶向生物制剂可显著降低OCS使用量，具有降低OCS累积毒性的潜力。糖皮质激素毒性指数（Glucocorticoid Toxicity Index，GTI）可系统评估OCS相关毒性；GTI总改善分数（Aggregate Improvement Score，AIS）是总毒性变化的双向测量指标，其最小临床重要差异值（MCID）为-10分。
目的：通过对接受生物制剂治疗的重度哮喘患者进行纵向评估，分析OCS相关毒性的变化轨迹和毒性改善的预测因素。
方法：89例重度患者在基线时、生物制剂治疗1年和3年后进行GTI评估。
结果：在3年中，日均泼尼松龙剂量持续下降[第1年6.9mg/天（4.0，9.4）vs第3年0.8mg/天（0.0，3.7），p<0.001]，OCS相关毒性持续下降[第3年AIS：-36分（-94，19），61%（54/89）的患者达到AIS MCID]。第1年和第3年的毒性变化结局呈显著正相关（p<0.001)。近一半（49%）的患者第1年和第3年末的AIS达到MCID，但29%的患者在这两个时间点的AIS均没有达到MCID。第1年毒性变化结果对3年后毒性变化的预测性为79%。毒性降低程度与OCS剂量减少不成比例，且未发现能够预测毒性降低的基线临床特征。
结论：接受生物制剂治疗3年后，61%的重度哮喘患者实现了临床显著的毒性改善。该队列1年后的毒性结局与纵向结局相关，这表明对部分患者来说，除了减少OCS，还需要额外的干预措施来降低OCS毒性发生率。
(四川大学华西医院呼吸与危重症医学科 谯猗丹1 王霁1 王刚1 译)
(The Journal of Allergy and Clinical Immunology: In Practice, In Press Corrected Proof, Published online: October 28, 2024. doi: 10.1016/j.jaip.2024.10.024. PMID: 39477016)
(The Journal of Allergy and Clinical Immunology: In Practice, In Press Corrected Proof, Published online: October 28, 2024. doi: 10.1016/j.jaip.2024.10.024. PMID: 39477016)
Longitudinal assessment of glucocorticoid toxicity reduction in patients with severe asthma treated with biologic therapies.
P Jane McDowell, PhD, John Busby, PhD, John H. Stone, MD, Claire A. Butler, PhD, Liam G. Heaney, MD
The Journal of Allergy and Clinical Immunology: In Practice, In Press Corrected Proof, Published online: October 28, 2024. doi: 10.1016/j.jaip.2024.10.024. PMID: 39477016
Abstract
Background: Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI aggregate improvement score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤ -10.
Objective: Longitudinal assessment of SA patients treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement.
Methods: 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy.
Results: At 3 years, daily prednisolone use continued to decrease (6.9 mg/day (4.0,9.4) year-1 v 0.8 mg/day (0.0,3.7) year-3, p<0.001), OCS-related toxicity continued to decline (AIS at 3yrs -36 (-94, 19), and 61% (54/89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at year-1 and year-3 (rho 0.65, p<0.001). Nearly half (49%) met the AIS MCID at both year-1 and 3, but 29% of the cohort did not meet the AIS MCID at either timepoint. Toxicity change at year-1 was predictive of toxicity change at year-3 for 79%. Toxicity reduction was not proportional to OCS reduction, there were no pre-biologics characteristics that predicted toxicity reduction.
Conclusions: After 3 years of biologic treatment, 61% of SA patients had clinically significant toxicity improvement. Individual toxicity outcomes at year-1 are associated with longitudinal outcomes suggesting that for some, additional interventions are needed alongside OCS-reduction to decrease morbidity.
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