Thomas G A, Rhodes J, Ragunath K, Mani V, Williams G T, Newcombe R G, Russell M A, Feyerabend C
Department of Gastroenterology, University Hospital of Wales, Cardiff, UK.
Eur J Gastroenterol Hepatol. 1996 Aug;8(8):769-76.
Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy.
To examine nicotine alone compared with prednisolone in active disease.
Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study.
Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor.
In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily.
溃疡性结肠炎在很大程度上是一种非吸烟者易患的疾病。既往对照试验表明，在活动性疾病中，经皮给予尼古丁联合5-氨基水杨酸有获益，但单独作为维持治疗时则无此效果。
比较单独使用尼古丁与泼尼松龙治疗活动性疾病的效果。
在一项随机、双盲研究中，61例活动性溃疡性结肠炎患者接受经皮尼古丁贴片或15mg泼尼松龙治疗6周。在治疗的前9天给予递增剂量的尼古丁；患者每日耐受剂量为15至25mg。大多数患者在入组时正在服用美沙拉嗪，在第10天停用；少数患者正在使用局部类固醇，在研究开始时停用。在基线、6周时或提前退出研究时进行临床、乙状结肠镜和组织学评估。症状记录在日记卡上，由临床医生进行整体临床评估。在整个研究过程中监测副作用以及血清尼古丁和可替宁浓度。
43例患者完成了6周试验；其中，尼古丁组19例中有6例乙状结肠镜检查完全缓解，而泼尼松龙组24例中有14例（P = 0.08）。在完成6周研究的患者中，尼古丁组和泼尼松龙组的圣马克评分（分别为P < 0.05和P < 0.01）、整体临床分级（两组均为P < 0.01）、便血（P < 0.05和P < 0.01）、腹痛（P < 0.05和P < 0.01）和乙状结肠镜评分（P < 0.01和P < 0.001）均有显著改善；组间差异倾向于支持泼尼松龙，但均未达到统计学意义。然而，在意向性分析中，除乙状结肠镜评分外，两组几乎没有明显的改善证据，在乙状结肠镜评分方面，泼尼松龙的改善明显大于尼古丁（P≤0.05）。尼古丁组的退出人数比泼尼松龙组多，分别为11例和7例（P = 0.23），因病情恶化退出的分别为6例和5例，因副作用退出的分别为5例和2例（P = 0.15）。尼古丁组报告的副作用比泼尼松龙组更频繁（平均每人1.47次发作）（平均0.61次；P = 0.03），最常见的副作用是恶心、头晕和震颤。
在那些成功完成6周研究的患者中，单独使用尼古丁在急性结肠炎中的获益似乎非常有限，且不如每日15mg泼尼松龙有效。
