第一组生物学降低了在患有全系统儿童关节炎的弃婴中葡萄糖分泌的比例

Carina Mihai
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摘要

背景:糖皮质激素暴露是系统性幼年特发性关节炎(sJIA)患儿发病率的重要驱动因素。我们确定了早期开始生物治疗(IL-1或IL-6抑制)对新发sJIA住院患者糖皮质激素暴露的影响。方法:利用来自52家三级儿童医院2008年至2019年的行政数据库的回顾性数据,模拟了一组实用的新发sJIA住院儿童(≤18岁)的生物启动试验(“伪试验”)。在每个伪试验中,对生物和非生物研究组的资格窗口、治疗分配和随访开始进行对齐。源人群中的患者可以在几个时间点满足资格标准。采用混合效应logistic回归来确定生物起始对院内糖皮质激素暴露的影响。结果:468名儿童符合资格标准,其中19%接受了生物治疗,没有事先或同时开始免疫调节药物。随着研究时间的延长,这一比例显著增加(p < 0.01)。1451名受试者被纳入4个伪试验,其中71人被分配到生物组,1380人被分配到非生物组。调整后,与非生物组相比,生物组中糖皮质激素启动的几率有降低的趋势(OR 0.39, 95% CI[0.13, 1.15])。结论:新发sJIA住院儿童的生物起始率随时间显著增加,可能与糖皮质激素暴露减少有关。越来越多地使用一线生物治疗可能导致临床相关的糖皮质激素依赖性治疗方法治疗相关不良反应的减少。
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First-line-Biologika reduzieren die Glukokortikoidexposition bei hospitalisierten Kindern mit systemischer juveniler idiopathischer Arthritis
Background: Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA. Methods: We emulated a pragmatic sequence of trials (“pseudo-trials”) of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children’s hospitals from 2008 to 2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure. Results: Four hundred sixty-eight children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p < 0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1380 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]). Conclusion: Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.
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