Korzenik Joshua R, Dieckgraefe Brian K, Valentine John F, Hausman Diana F, Gilbert Mark J
Inflammatory Bowel Disease Center, Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
N Engl J Med. 2005 May 26;352(21):2193-201. doi: 10.1056/NEJMoa041109.
Sargramostim, granulocyte-macrophage colony-stimulating factor, a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Preliminary studies suggest sargramostim may have activity in Crohn's disease. To evaluate this novel therapeutic approach, we conducted a randomized, placebo-controlled trial.
Using a 2:1 ratio, we randomly assigned 124 patients with moderate-to-severe active Crohn's disease to receive 6 mug of sargramostim per kilogram per day or placebo subcutaneously for 56 days. Antibiotics and aminosalicylates were allowed; immunosuppressants and glucocorticoids were prohibited. The primary end point was a clinical response, defined by a decrease from baseline of at least 70 points in the Crohn's Disease Activity Index (CDAI) at the end of treatment (day 57). Other end points included changes in disease severity and the health-related quality of life and adverse events.
There was no significant difference in the rate of the primary end point of a clinical response defined by a decrease of at least 70 points in the CDAI score on day 57 between the sargramostim and placebo groups (54 percent vs. 44 percent, P=0.28). However, significantly more patients in the sargramostim group than in the placebo group reached the secondary end points of a clinical response defined by a decrease from baseline of at least 100 points in the CDAI score on day 57 (48 percent vs. 26 percent, P=0.01) and of remission, defined by a CDAI score of 150 points or less on day 57 (40 percent vs. 19 percent, P=0.01). The rates of either type of clinical response and of remission were significantly higher in the sargramostim group than in the placebo group on day 29 of treatment and 30 days after treatment. The sargramostim group also had significant improvements in the quality of life. Mild-to-moderate injection-site reactions and bone pain were more common in the sargramostim group, and three patients in this group had serious adverse events possibly or probably related to treatment.
This study was negative for the primary end point, but findings for the secondary end points suggest that sargramostim therapy decreased disease severity and improved the quality of life in patients with active Crohn's disease.
沙格司亭，即粒细胞-巨噬细胞集落刺激因子，一种造血生长因子，可刺激肠道固有免疫系统的细胞。初步研究表明沙格司亭可能对克罗恩病有治疗作用。为评估这种新的治疗方法，我们进行了一项随机、安慰剂对照试验。
按照2:1的比例，我们将124例中度至重度活动性克罗恩病患者随机分为两组，分别接受每天每千克体重6微克沙格司亭皮下注射或安慰剂皮下注射，共56天。允许使用抗生素和氨基水杨酸类药物；禁止使用免疫抑制剂和糖皮质激素。主要终点为临床反应，定义为治疗结束时（第57天）克罗恩病活动指数（CDAI）较基线下降至少70分。其他终点包括疾病严重程度的变化、健康相关生活质量以及不良事件。
沙格司亭组和安慰剂组在第57天CDAI评分下降至少70分所定义的临床反应这一主要终点的发生率上无显著差异（54%对44%，P = 0.28）。然而，沙格司亭组达到次要终点的患者明显多于安慰剂组，次要终点包括第57天CDAI评分较基线下降至少100分所定义的临床反应（48%对26%，P = 0.01）以及第57天CDAI评分为150分或更低所定义的缓解（40%对19%，P = 0.01）。在治疗第29天和治疗后30天，沙格司亭组的任何一种临床反应和缓解率均显著高于安慰剂组。沙格司亭组的生活质量也有显著改善。沙格司亭组轻度至中度注射部位反应和骨痛更为常见，该组有3例患者发生了可能或很可能与治疗相关的严重不良事件。
本研究的主要终点为阴性，但次要终点的结果表明沙格司亭治疗可降低活动性克罗恩病患者的疾病严重程度并改善生活质量。
