Department of Gastroenterology, University of Liverpool, Liverpool, UK.
Gut. 2011 Nov;60(11):1520-6. doi: 10.1136/gut.2010.225482. Epub 2011 Apr 6.
To assess the safety and efficacy of the B lymphocyte (anti-CD20) antibody, rituximab, in the treatment of steroid-resistant moderately active ulcerative colitis (UC).
A double-blinded, randomised controlled trial with a 2:1 ratio of treatment:placebo (phase II) was carried out in the setting of a University teaching hospital. The subjects comprised 24 patients with moderately active UC who have either failed to respond to conventional corticosteroid therapy or who have relapsed during corticosteroid withdrawal. Five of 8 placebo-treated patients and 12 of 16 rituximab-treated patients were receiving azathioprine, 6-mercaptopurine or methotrexate. Two infusions of rituximab 1 g in 500 ml of 0.9% saline intravenously over 4 h (n=16) or saline placebo (n=8) were given at 0 and 2 weeks. Patients still receiving corticosteroids on entry (placebo group 7/8; rituximab group 14/16) continued a standard steroid tapering regimen. The primary end point was remission (Mayo score ≤ 2) at 4 weeks. Secondary end points included response (Mayo score reduced ≥ 3) at 4 and 12 weeks.
Mayo score at entry was higher in rituximab-treated patients (mean 9.19; 95% CI 8.31 to 10.06) than for placebo patients (7.63; 6.63 to 8.62, p=0.03). At week 4 only 1/8 placebo-treated patients and 3/16 rituximab-treated patients were in remission (p=1.0), but 8/16 rituximab-treated patients had responded compared with 2/8 placebo-treated patients, with a median reduction in Mayo score of 2.5 (rituximab) compared with 0 (placebo; p=0.07). This response was only maintained to week 12 in 4/16. Mucosal healing was seen at week 4 in 5/16 rituximab-treated patients and 2/8 placebo-treated patients (non-significant). Rituximab was well tolerated, with one chest infection, three mild infusion reactions plus one case of (probably unrelated) non-fatal pulmonary embolism. CONCLUSIONS Rituximab has no significant effect on inducing remission in moderately active UC not responding to oral steroids. There was a possible short-term response that was not sustained. Rituximab is well tolerated in UC.
NCT00261118.
评估 B 淋巴细胞（抗 CD20）抗体利妥昔单抗治疗激素抵抗性中度活动溃疡性结肠炎（UC）的安全性和有效性。
在一所大学教学医院进行了一项双盲、随机对照试验，治疗组与安慰剂组的比例为 2:1（二期）。研究对象包括 24 例对常规皮质类固醇治疗无反应或在皮质类固醇撤药期间复发的中度活动 UC 患者。8 例安慰剂治疗组中有 5 例和 16 例利妥昔单抗治疗组中有 12 例正在接受硫唑嘌呤、6-巯基嘌呤或甲氨蝶呤治疗。两组患者分别静脉输注利妥昔单抗 1g（溶于 500ml 生理盐水）4 小时（16 例）或生理盐水安慰剂（8 例），在 0 周和 2 周时各输注一次。进入研究时仍在接受皮质激素治疗的患者（安慰剂组 7/8；利妥昔单抗组 14/16）继续进行标准的皮质类固醇逐渐减量方案。主要终点是 4 周时缓解（Mayo 评分≤2）。次要终点包括 4 周和 12 周时的应答（Mayo 评分降低≥3）。
利妥昔单抗治疗组患者的 Mayo 评分（9.19；95%CI8.31 至 10.06）高于安慰剂组（7.63；6.63 至 8.62，p=0.03）。在第 4 周时，只有 1/8 例安慰剂治疗组和 3/16 例利妥昔单抗治疗组的患者达到缓解（p=1.0），但 8/16 例利妥昔单抗治疗组的患者有应答，而安慰剂组仅 2/8 例患者有应答，利妥昔单抗组 Mayo 评分中位数降低 2.5 分，而安慰剂组降低 0 分（p=0.07）。这种应答仅在 4/16 例患者中持续到第 12 周。在第 4 周时，16 例利妥昔单抗治疗组中有 5 例和 8 例安慰剂治疗组中有 2 例患者出现黏膜愈合（无显著性差异）。利妥昔单抗耐受性良好，有 1 例胸部感染，3 例轻度输液反应，1 例可能与治疗无关的非致命性肺栓塞。
利妥昔单抗对口服皮质激素治疗无反应的中度活动 UC 患者诱导缓解无显著作用。可能存在短期应答，但未能持续。利妥昔单抗在 UC 中耐受良好。
NCT00261118。
