Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis
Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis
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DOI：
10.1136/gut.2010.225482
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发表时间：
2011-11-01
期刊：
影响因子：
24.5
通讯作者：
Rhodes, Jonathan M.
中科院分区：
文献类型：
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作者：
Leiper, Keith;Martin, Kate;Rhodes, Jonathan M.
目的评价B淋巴细胞（抗CD 20）抗体利妥昔单抗（rituximab）治疗激素耐药中度活动期溃疡性结肠炎（UC）的安全性和有效性。受试者包括24例中度活动性UC患者，这些患者对传统糖皮质激素治疗无效或在糖皮质激素停药期间复发。5/8例安慰剂治疗患者和12/16例利妥昔单抗治疗患者正在接受硫唑嘌呤、6-巯基嘌呤或甲氨蝶呤治疗。在第0周和第2周，给予利妥昔单抗1 g溶于500 ml 0.9%生理盐水中静脉输注4 h（n=16）或生理盐水安慰剂（n=8）。入组时仍接受皮质类固醇的患者（安慰剂组7/8;利妥昔单抗组14/16）继续标准类固醇减量方案。主要终点是缓解（马约评分= 3）在4和12 wk.Results马约评分在进入利妥昔单抗治疗组（平均9.19; 95%CI 8.31至10.06）高于安慰剂组（7.63; 6.63至8.62，p=0.03）。在第4周，仅1/8例安慰剂治疗患者和3/16例利妥昔单抗治疗患者缓解（p=1.0），但与2/8例安慰剂治疗患者相比，8/16例利妥昔单抗治疗患者有应答，马约评分中位数降低2.5（利妥昔单抗），与0（安慰剂; p=0.07）相比。该反应仅在4/16例中维持至第12周。第4周时，在5/16例利妥昔单抗治疗患者和2/8例安慰剂治疗患者中观察到粘膜愈合（无显著性）。利妥昔单抗耐受性良好，一个胸部感染，三个轻微的输液反应，加上一个案件（可能无关）非致命性肺embolize.Conclusions利妥昔单抗诱导缓解中度活动性UC没有响应口服类固醇没有显着的效果。可能有一种短期反应，但这种反应没有持续下去。利妥昔单抗在UC中耐受良好。
Objective 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).Methods 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 = 3) at 4 and 12 weeks.Results 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-teated 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.