Kucharzik Torsten, Lemmnitz Gunter, Abels Christoph, Maaser Christian
*Department of Gastroenterology, Lüneburg Hospital, University of Hamburg, Lüneburg, Germany; and †Dr. August Wolff GmbH & Co. KG, Arzneimittel, Bielefeld, Germany.
Inflamm Bowel Dis. 2017 Feb;23(2):261-271. doi: 10.1097/MIB.0000000000001000.
K(D)PT showed marked anti-inflammatory properties in preclinical studies and exhibited very low toxicity in phase I and preclinical trials. In this study, efficacy and safety of oral K(D)PT were evaluated in patients with mild-to-moderate active ulcerative colitis.
A multicenter, randomized, double-blind, phase IIa trial was performed comparing add-on oral K(D)PT twice a day (20, 50, or 100 mg) with placebo in patients with mild-to-moderate active ulcerative colitis on baseline medication. The primary objective was to determine the difference in time to sustained improvement in colitis activity index (CAI) of ≥50% at week 8 between pooled K(D)PT group and placebo. Secondary endpoints included remission rates and CAI response at different time points.
Compared with placebo, K(D)PT (pooled group) resulted in significantly higher proportions of patients in remission at 2 and 4 weeks, (2 wk: P = 0.0349; 4 wk: P = 0.0278) and a significantly higher proportion of patients with CAI response at week 8 (P = 0.0434). K(D)PT (pooled group) met the primary endpoint after additional analyses. Because of high placebo response rates, subgroup analyses tried to identify patients with unquestionably active and more severe, but still moderate, disease (CAI score ≥9 or taking more than one concomitant medication). These subgroups showed earlier and statistically significant CAI responses to K(D)PT versus placebo. All doses of K(D)PT were well tolerated.
Despite a very high placebo rate after week 4, study data in this preliminary trial strongly suggest that add-on K(D)PT is efficacious in patients with mild-to-moderate ulcerative colitis. Moreover, K(D)PT showed an excellent safety profile.
K(D)PT在临床前研究中显示出显著的抗炎特性，并且在I期和临床前试验中表现出极低的毒性。在本研究中，对轻度至中度活动性溃疡性结肠炎患者口服K(D)PT的疗效和安全性进行了评估。
进行了一项多中心、随机、双盲、IIa期试验，将基线用药的轻度至中度活动性溃疡性结肠炎患者每日两次口服K(D)PT（20、50或100毫克）与安慰剂进行比较。主要目标是确定在第8周时，联合K(D)PT组与安慰剂组之间结肠炎活动指数（CAI）持续改善≥50%的时间差异。次要终点包括不同时间点的缓解率和CAI反应。
与安慰剂相比，K(D)PT（联合组）在第2周和第4周时缓解的患者比例显著更高（第2周：P = 0.0349；第4周：P = 0.0278），并且在第8周时CAI反应的患者比例显著更高（P = 0.0434）。经过额外分析，K(D)PT（联合组）达到了主要终点。由于安慰剂反应率较高，亚组分析试图识别出病情明确活跃且更严重但仍为中度的患者（CAI评分≥9或同时服用一种以上伴随药物）。这些亚组显示，与安慰剂相比，K(D)PT对CAI的反应更早且具有统计学意义。所有剂量的K(D)PT耐受性良好。
尽管在第4周后安慰剂率非常高，但该初步试验的研究数据强烈表明，联合使用K(D)PT对轻度至中度溃疡性结肠炎患者有效。此外，K(D)PT显示出极佳的安全性。
