Gordon F H, Lai C W, Hamilton M I, Allison M C, Srivastava E D, Fouweather M G, Donoghue S, Greenlees C, Subhani J, Amlot P L, Pounder R E
Centre for Gastroenterology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, England.
Gastroenterology. 2001 Aug;121(2):268-74. doi: 10.1053/gast.2001.26260.
BACKGROUND & AIMS: alpha4 integrins are important mediators of leukocyte migration across vascular endothelium. This pilot placebo-controlled study aimed to assess the safety and efficacy of natalizumab, a recombinant humanized monoclonal antibody to alpha4 integrin, in patients with mild to moderately active Crohn's disease.
Thirty patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =151 and < or =450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization. The study's primary endpoint was change in CDAI at week 2.
At week 2, the CDAI decreased significantly from baseline after infusion of natalizumab (mean 45 points) but not placebo (mean 11 points). Seven (39%) natalizumab-treated patients achieved remission at week 2, compared with 1 (8%) treated with placebo. In contrast, 4 (33%) of the placebo-treated patients required rescue medication by week 2, compared with 2 (11%) natalizumab-treated patients. Significant increases in circulating B and T lymphocytes were detected only after natalizumab administration. The frequency of commonly reported adverse events did not differ significantly between groups.
A single 3-mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal. Elevated circulating lymphocyte levels after natalizumab suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation.
α4整合素是白细胞跨血管内皮迁移的重要介质。这项初步的安慰剂对照研究旨在评估那他珠单抗（一种针对α4整合素的重组人源化单克隆抗体）对轻至中度活动性克罗恩病患者的安全性和疗效。
30例活动性克罗恩病患者（克罗恩病活动指数[CDAI]≥151且≤450）通过双盲随机分组接受3mg/kg那他珠单抗输注（n = 18）或安慰剂输注（n = 12）。研究的主要终点是第2周时CDAI的变化。
在第2周时，输注那他珠单抗后CDAI较基线显著下降（平均45分），而安慰剂组则无显著下降（平均11分）。7例（39%）接受那他珠单抗治疗的患者在第2周时达到缓解，而接受安慰剂治疗的患者中只有1例（8%）达到缓解。相比之下，2例（11%）接受那他珠单抗治疗的患者在第2周时需要抢救药物，而接受安慰剂治疗的患者中有4例（33%）需要。仅在给予那他珠单抗后检测到循环B淋巴细胞和T淋巴细胞显著增加。两组中常见不良事件的发生率无显著差异。
克罗恩病患者对单次3mg/kg那他珠单抗输注耐受性良好，尽管所用剂量可能并非最佳。那他珠单抗治疗后循环淋巴细胞水平升高提示淋巴细胞转运受阻。那他珠单抗治疗活动性克罗恩病值得进一步研究。
