Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Box 85500, 3508 GA Utrecht, The Netherlands.
Rheumatology (Oxford). 2012 Jun;51 Suppl 4:iv9-13. doi: 10.1093/rheumatology/kes086.
DMARDs aim to improve long-term prognosis of RA, as indicated by reduced progression of radiographic damage and maintenance of function. However, it may be more appropriate to consider disease-modifying strategies rather than drugs alone. Despite the challenges (e.g. lack of standard outcome measures, poor reporting of dose levels), a systematic review of 15 studies involving more than 1400 patients showed that glucocorticoid treatment for 1-2 years slowed radiographic progression compared with control treatment. Evidence for longer term disease-modifying benefits of glucocorticoids comes from individual studies with extended follow-up. In the Utrecht study, patients with early RA originally assigned to prednisone 10 mg/day for 2 years and then tapered off the therapy showed significantly less radiographic progression at follow-up after a further 3 years than patients originally assigned placebo, with no significant difference in the use of synthetic DMARD therapy. In the combination therapy in early RA (COBRA) study, patients with newly diagnosed RA treated with glucocorticoid (starting with 60 mg/day, quickly reduced to 7.5 mg/day for weeks 7-28 and subsequently stopped), MTX up to week 40 and SSZ showed significantly decreased radiographic progression compared with those treated with SSZ alone. The benefits of short-term combination therapy on disease progression were still apparent at 5-year and 11-year follow-up. In conclusion, there is clear evidence that treatment regimens including low-dose glucocorticoids given early in RA slow radiographic progression, meeting the definition of a DMARD. Furthermore, the evidence suggests that such treatment strategies favourably alter the disease course even after glucocorticoid discontinuation.
DMARDs 的目标是改善 RA 的长期预后,这表现为放射学损伤的进展减少和功能的维持。然而,考虑疾病修正策略可能更为恰当,而不仅仅是药物。尽管存在挑战(例如缺乏标准的结局测量、剂量水平报告不佳),但对 15 项涉及 1400 多名患者的研究进行的系统评价表明,与对照组相比,1-2 年的糖皮质激素治疗可减缓放射学进展。糖皮质激素在更长时间内对疾病具有修正作用的证据来自于随访时间延长的个别研究。在乌得勒支研究中,最初被分配给泼尼松 10mg/天治疗 2 年,然后逐渐减少治疗的早期 RA 患者,与最初被分配安慰剂的患者相比,在进一步随访 3 年后的放射学进展明显较少,而在合成 DMARD 治疗的使用方面没有显著差异。在早期 RA 的联合治疗(COBRA)研究中,与单独接受 SSZ 治疗的患者相比,新诊断为 RA 的患者接受糖皮质激素(起始剂量为 60mg/天,迅速减少至第 7-28 周的 7.5mg/天,随后停止)、MTX 至第 40 周和 SSZ 的患者放射学进展明显减少。短期联合治疗对疾病进展的益处在 5 年和 11 年随访时仍然明显。总之,有明确的证据表明,RA 早期使用低剂量糖皮质激素的治疗方案可减缓放射学进展,符合 DMARD 的定义。此外,证据表明,即使在停止使用糖皮质激素后,此类治疗策略也有利于改变疾病进程。