School of Immunity and Infection, University of Birmingham, Birmingham, UK.
Ann Rheum Dis. 2012 Jun;71(6):955-60. doi: 10.1136/annrheumdis-2011-200477. Epub 2011 Nov 29.
The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study.
Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised.
Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs.
Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
先前报道的一项关于共识方案脉冲环磷酰胺的随机对照试验表明，当与相同的糖皮质激素方案联合使用时，它与每日口服（DO）环磷酰胺一样有效，可诱导抗中性粒细胞胞质抗体相关性系统性血管炎缓解（CYCLOPS 研究（每日口服与脉冲环磷酰胺治疗抗中性粒细胞胞质抗体相关性系统性血管炎的随机试验发表于 de groot K, harper L 等人的《Ann Int Med》2009 年））。该研究检测复发差异的能力有限。本研究描述了 CYCLOPS 研究中患者的长期结局。
长期结局从先前招募到 CYCLOPS 试验的 148 名患者中回顾性确定。从医生记录中回顾性收集了生存、复发、免疫抑制治疗、癌症发病率、骨折、血栓栓塞性疾病和心血管发病率的数据。所有患者均根据其随机分组进行分析。
中位随访时间为 4.3 年（IQR，2.95-5.44 年）。两组之间的生存率无差异（p=0.92）。15 名（20.8%）DO 和 30 名（39.5%）脉冲患者至少有一次复发。DO 组的复发风险明显低于脉冲组（HR=0.50，95%CI 0.26 至 0.93；p=0.029）。尽管脉冲治疗患者的复发风险增加，但研究结束时肾功能无差异（p=0.82）。两种治疗组之间的不良事件无差异。
脉冲环磷酰胺与更高的复发风险相关，而不是 DO 环磷酰胺。然而，这与死亡率或长期发病率的增加无关。尽管该研究是回顾性的，但原始试验中有 90%的患者返回了数据。
