Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S42-5. Epub 2011 Oct 21.
Glucocorticoids (GCs) are widely used in clinical medicine because of their anti-inflammatory and immunosuppressive effects. However, these agents have a considerable potential for adverse effects, especially if used in high doses. The currently most advanced approach to improve the risk-benefit ratio of GCs is low-dose prednisone chronotherapy with modified release (MR) prednisone timing drug release to chronobiological rhythms. In RA, the circadian rhythms of pain, stiffness and functional disability show maximum symptoms in the early morning hours, which is preceded by elevated levels of pro-inflammatory cytokines, in particular interleukin 6. It was hypothesised that preventing the nocturnal rise of pro-inflammatory cytokines by GC therapy is more effective than treating established symptoms in the morning. As waking in the night for tablet intake is impracticable, modified release (MR) prednisone was developed, which releases prednisone approximately four hours after ingestion (i.e. at approximately 2 am if taken at 10 pm bedtime). Data from two large-scale trials in rheumatoid arthritis (RA) (CAPRA-1 and 2) document that MR prednisone has greater efficacy for long-term, low-dose glucocorticoid treatment in patients with RA, with a significant reduction in morning joint stiffness, in addition to all known therapeutic effects with conventional prednisone and a similar safety profile without additional suppression of hypothalamic-pituitary-adrenal (HPA) axis. For patients with RA on low to medium doses of prednisone, especially those who continue to experience a long duration of morning stiffness, MR prednisone appears a valuable additional treatment option.
糖皮质激素（GCs）因其抗炎和免疫抑制作用而在临床医学中广泛应用。然而，这些药物有很大的潜在不良反应风险，特别是如果使用大剂量。目前，改善 GC 风险效益比的最先进方法是采用低剂量泼尼松晨释疗法，即通过改变释放时间使泼尼松的释放符合生理节律。在类风湿关节炎（RA）中，疼痛、僵硬和功能障碍的昼夜节律在清晨达到最大值，在此之前，促炎细胞因子水平升高，尤其是白细胞介素 6。有人假设，通过 GC 治疗预防夜间促炎细胞因子的升高比在早上治疗已有的症状更有效。由于夜间起床服药不切实际，因此开发了控释（MR）泼尼松，这种药物在摄入后大约四小时释放泼尼松（如果在晚上 10 点睡前服用，则大约在凌晨 2 点释放）。两项大型类风湿关节炎（RA）临床试验（CAPRA-1 和 2）的数据表明，MR 泼尼松在 RA 患者的长期低剂量糖皮质激素治疗中具有更高的疗效，除了常规泼尼松的所有已知治疗效果外，还能显著减少早晨关节僵硬，同时具有相似的安全性，不会进一步抑制下丘脑-垂体-肾上腺（HPA）轴。对于接受低至中等剂量泼尼松治疗的 RA 患者，尤其是那些持续经历长时间早晨僵硬的患者，MR 泼尼松似乎是一种有价值的额外治疗选择。
