Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine.     

5-氨基水杨酸维持治疗溃疡性结肠炎114例

目的:评估5-氨基水杨酸(5-ASA)对溃疡性结肠炎(UC)缓解期患者维持治疗及影响UC复发的相关因素.方法:回顾性分析2004-01/2010-08在北京大学第一医院消化内科就诊的114例缓解期UC患者的临床资料,纳入分析病例114例.其中,男64例,女50例,年龄16-76岁.结果:选择应用5-ASA诱导缓解治疗病例75例(65.8%).结果显示:(1)UC复发与性别无关;(2)病程>5年的UC患者复发率显著高于病程≤5年的UC患者(62.1%vs35.7%,P>0.05);(3)轻度UC患者5-ASA维持治疗剂量>2g/d者复发率显著低于≤2g/d者(10%vs33.3%,P<0.05);(4)轻度UC患者复发率显著低于中度和重度患者(24.6%vs83.3%,80.6%,P<0.05);(5)直肠型UC患者复发率(19.2%)较低;(6)诱导缓解治疗达到黏膜愈合患者的复发率显著低于未达到黏膜愈合的患者(4.8%vs89.6%,P<0.05);(7)UC患者诱导缓解后第2年始复发率随时间逐年上升.结论:黏膜愈合及疾病活动程度是影响UC复发率的重要因素,5-ASA是轻-中度UC维持缓解治疗的首选药物,5-...     

国产5-氨基水杨酸肠溶片治疗溃疡性结肠炎多中心临床研究

目的　评价国产 5 氨基水杨酸 (5 ASA)肠溶片治疗溃疡性结肠炎 (UC)的疗效和安全性及该药的口服吸收情况。方法　采用多中心、随机、双盲、双模拟和对照方案 ,将 1 2 9例UC患者随机分为5 ASA肠溶片试验组 (6 5例 ,2 .4 g/d)和水杨酸偶氮磺胺吡啶 (SASP)对照组 (6 4例 ,4 .0g/d) ,疗程均为6周。治疗第 8天 ,随机抽取试验组 1 3例和对照组 1 2例UC患者血清 ,应用高效液相色谱分析法检测血清 5 ASA及其代谢产物Ac 5 ASA的稳态血药浓度。对两组患者治疗前后的临床症状、粪便检查和肠镜检查的情况进行比较 ,并记录治疗过程中的不良反应。结果　实际完成研究者 1 2 0例 (5 ASA组 6 1例 ,SASP组 5 9例 ) ,两组各有 4例失访 ,SASP组有 1例因严重胃肠道不良反应中途退出。 5 ASA肠溶片组和SASP组治疗UC的总有效率分别为 70 .0 5 %和 6 7.79% ,两组间差异无显著性 (P >0 .0 5 ) ,5 ASA肠溶片的完全缓解率明显高于SASP (2 9.5 1 %比 1 3.31 % ,P <0 .0 5 )。 5 ASA肠溶片组和SASP组的不良反应分别为 1 1 .4 8%和 2 3.33%。 5 ASA组和SASP组的血清 5 ASA浓度分别为 (0 .0 32± 0 .0 0 8) μg/ml和 (0 .0 4 1± 0 .0 0 5 ) μg/ml(P >0 .0 5 )。 结论　 5 ASA肠溶片治疗UC总有效率与SASP相仿 ,但对UC的完     

Retrograde distribution of a new 5-aminosalicylic acid enema in patients with ulcerative colitis.

Retrograde colonic distribution of a new 4 g 5-aminosalicylic acid enema (mesalazine) was investigated in seven patients with ulcerative colitis, five of whom were in remission. The enema was labeled with 99m-technetium and imaged by a gamma camera. A median of 86 percent (range 57-90) of the enema had spread beyond the rectum during the first two hours after administration. In four of the five examined patients with left-sided ulcerative colitis, the diseased mucosa was covered within the first 4 hours. In the fifth patient, with involvement of the descending colon, the enema did not spread beyond the very tortuous sigmoid colon 4 or even 8 hours after enema administration.     

Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis （UC） diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram （ECG） revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram （ECHO） revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries （〈 3.5 mm）. Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.     

Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis

BACKGROUND AND AIMS: There are limited evidence based data concerning the use of azathioprine in ulcerative colitis. We aimed to compare the efficacy of azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid dependent ulcerative colitis. METHODS: Seventy two patients with steroid dependent ulcerative colitis were admitted to this investigator-blind study. Steroid dependence was defined as a requirement for steroid therapy > or =10 mg/day during the preceding six months, with at least two attempts to discontinue the medication. The disease had to be clinically and endoscopically active at study entry, and all patients were taking systemic prednisolone (40 mg/day). Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5-aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of the treatment was defined as (1) success, indicating induction of clinical and endoscopic remission and steroid discontinuation, or (2) failure, indicating the absence of clinical and endoscopic remission and therefore the need for at least one further cycle of systemic steroids to control symptoms, apart from the initial one, or colectomy. RESULTS: Significantly more patients in the azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic remission, and discontinued steroid therapy, both in the intention to treat (azathioprine v 5-aminosalicylic acid: 19/36 patients (53%) v 7/36 (21%); odds ratio (OR) 4.78 (95% confidence interval (CI) 1.57-14.5)) and per protocol (azathioprine v 5-aminosalicylic acid: 19/33 patients (58%) v 7/34 (21%); OR 5.26 (95% CI 1.59-18.1)) analysis. CONCLUSIONS: Azathioprine is significantly more effective than 5-aminosalicylic acid in inducing clinical and endoscopic remission and avoiding steroid requirement in the treatment of steroid dependent ulcerative colitis.     

Acute pericarditis associated with 5-aminosalicylic acid (5-ASA) treatment for severe active ulcerative colitis

A 17-year-old male who had been diagnosed with ulcerative colitis was prescribed 80 mg prednisolone and 1,500 mg 5-aminosalicylic acid (5-ASA) per day. Two weeks after initiating therapy, he was referred to our hospital for evaluation of chest pain and high fever. Electrocardiography (ECG) showed ST elevation in limb and precordial leads. Chest pain with high fever and ECG changes were resolved after 5-ASA was discontinued. Three weeks later, the administration of a low dose of 5-ASA was associated with the immediate recurrence of pericarditis associated with chest pain, suggesting a hypersensitive reaction to 5-ASA in this patient.     

Comparison of bismuth citrate and 5-aminosalicylic acid enemas in distal ulcerative colitis: a controlled trial.

An enema that contained a complex of bismuth citrate and polyacrylate was compared with 5-aminosalicylic acid (5-ASA) enemas for treatment of distal ulcerative colitis. The multicentre trial involving 63 patients was randomised and double blind with enemas given over four weeks; clinical, sigmoidoscopic, and histological assessments were made. Improvements were seen in both treatment groups. Clinical remission was seen in 18 of 32 patients treated with 5-ASA and 12 of 31 patients treated with bismuth citrate-carbomer (chi 2 1.94; p = 0.16). Sigmoidoscopic remission occurred in 20 of 32 patients in the 5-ASA group and 15 of 31 patients given bismuth (chi 2 1.27; p = 0.26). Improvement of rectal biopsy histology by at least one grade was seen in 16 of 32 patients in the 5-ASA group and 14 of 31 patients with bismuth (chi 2 0.15; p = 0.70). Analysis of covariance gave no significant difference between groups, although there was a trend favouring 5-ASA. There was no evidence of bismuth accumulation during the trial. Bismuth enemas may offer a new therapeutic option in distal ulcerative colitis.     

Acute pancreatitis secondary to 5-aminosalicylic acid therapy in a patient with ulcerative colitis.

Therapy with oral 5-aminosalicylic acid (5-ASA) for ulcerative colitis has been reported to be effective and safe. We describe a case of biochemically proven mild acute pancreatitis occurring after 9 d of oral 5-ASA therapy for ulcerative colitis. A hypersensitivity mechanism seemed to be involved in the development of pancreatitis probably owing to erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for early diagnosis of pancreatitis in patients with ulcerative colitis receiving 5-ASA administration. This is the first report of acute pancreatitis developed by oral 5-ASA therapy for the treatment of ulcerative colitis in the literature of Japan.     

Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial

BACKGROUND & AIMS: Ulcerative colitis is most common in Western industrialized countries. Inflammatory bowel disease is uncommon in developing countries where helminths are frequent. People with helminths have an altered immunological response to antigens. In animal models, helminths prevent or improve colitis by the induction of regulatory T cells and modulatory cytokines. This study determined the efficacy and safety of the helminth Trichuris suis in therapy of ulcerative colitis. METHODS: This was a randomized, double blind, placebo-controlled trial conducted at the University of Iowa and select private practices. Trichuris suis ova were obtained from the US Department of Agriculture. The trial included 54 patients with active colitis, defined by an Ulcerative Colitis Disease Activity Index of > or =4. Patients were recruited from physician participants and were randomly assigned to receive placebo or ova treatment. Patients received 2500 Trichuris suis ova or placebo orally at 2-week intervals for 12 weeks. RESULTS: The primary efficacy variable was improvement of the Disease Activity Index to > or =4. After 12 weeks of therapy, improvement according to the intent-to-treat principle occurred in 13 of 30 patients (43.3%) with ova treatment compared with 4 of 24 patients (16.7%) given placebo (P = .04). Improvement was also found with the Simple Index that was significant by week 6. The difference in the proportion of patients who achieved an Ulcerative Colitis Disease Activity Index of 0-1 was not significant. Treatment induced no side effects. CONCLUSIONS: Ova therapy seems safe and effective in patients with active colitis.     

Oral and topical 5-aminosalicylic acid (mesalazine) in inducing and maintaining remission in mild-moderate relapse of ulcerative colitis: one-year randomised multicentre trial

BACKGROUND: The association of oral 5-aminosalicylic acid (mesalazine) and enema is effective in treatment of mild-moderate forms of ulcerative colitis. However no study has been aimed at determining optimal duration of this association in active ulcerative colitis. AIM: To determine whether longer duration of therapy: 1. increases the rate of patients achieving remission, and 2. reduces relapse rate during the maintenance period in patients in remission. PATIENTS AND METHODS: A total of 149 patients, (89 male, 60 female), were randomly assigned to a regimen with 5-aminosalicylic acid tablets 2.4 g/day associated with 5-aminosalycilic enema 2 g/day for a 4-week (n = 73) or 8-week regimen (n = 76). After this acute therapy, patients were submitted to clinical, endoscopic and histological examinations and those in remission were assigned to a follow-up (maintenance) period with oral mesalazine alone at a dosage of 1.2 g/day. A clinical visit, including laboratory tests, at 6 months and an endoscopic-histological control at 12 months were carried out to exclude symptoms and endoscopic-histological signs of activity. Relapse of disease, i.e., presence of clinical symptoms or abnormal laboratory tests, was confirmed by endoscopy and histology. RESULTS: At end of acute phase, clinical, endoscopic and histological remission was comparable in the two groups: 42/76 (55%), in the 4-week, and 47/73 patients (64%), in the 8-week regimen. No difference was found stratifying patients according to extension of disease. Of these 89 patients in remission, 75 (34 from 4-week regimen; 41 from 8-week regimen) completed 12 months' follow-up. At end of follow-up, a similar percentage of patients in the 4-week regimen (50%) and 8-week regimen (51%) were still in remission. No significant difference between cumulative relapse rates of the two groups was found. Stratifying patients according to extension of disease, in the 8-week regimen group, those with left-sided colitis showed a higher remission rate than that of patients with diffuse colitis (66% versus 35%, p < 0.05). All regimens were well tolerated by most patients during the entire study period. CONCLUSIONS: An additional 4 weeks of topical treatment does not increase the remission rate in patients with mild-moderate active ulcerative colitis but seems to reduce the probability of relapse in patients with left-sided colitis.     

Steady-state pharmacokinetics of a new 4-gram 5-aminosalicylic acid retention enema in patients with ulcerative colitis in remission.

The pharmacokinetic profile of a new 4-g 5-aminosalicyclic acid (5-ASA) retention enema, Mesasal, was investigated. Nine patients with ulcerative colitis in remission and one patient with mild disease activity received one enema for seven consecutive nights. They were admitted to hospital for administration of the eighth enema. Plasma concentration and urinary excretion of 5-ASA and acetyl-5-aminosalicyclic acid (Ac-5-ASA) were studied for 45 h and faecal excretion for 24 h after administration of the last enema. The median peak plasma concentration of 5-ASA was 0.92 (range, 0.59-1.87) micrograms/ml at a median of 11 h after administration, and of Ac-5-ASA 1.62 (range, 1.03-4.36) micrograms/ml at a median of 12 h after administration. On average, the plasma concentration of Ac-5-ASA was almost twice that of 5-ASA at each sampling period. At 24 h after administration the median plasma concentration for 5-ASA was 0.12 (range, 0-0.77) micrograms/ml and for Ac-5-ASA 0.36 (range, 0.01-1.6) micrograms/ml. At 45 h after administration low levels of both 5-ASA (less than 0.2 micrograms/ml) and Ac-5-ASA (less than 0.3 microgram/ml) were noted in two patients, low levels of only Ac-5-ASA (less than 0.1 microgram/ml) in two patients, and neither 5-ASA nor Ac-5-ASA in the other six patients. All patients had detectable urinary levels of both 5-ASA and Ac-5-ASA during the first 4 h after administration. Median urinary recovery during 45 h was 12.6% (range, 5.6-22.2%), indicating a low absorption at steady-state conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute pancreatitis in a child with idiopathic ulcerative colitis on long-term 5-aminosalicylic acid therapy.

Acute pancreatitis is a rare but known complication of inflammatory bowel disease in adults. In children, only a few cases with this complication have been reported. We describe a 10-year-old boy with ulcerative colitis who developed acute pancreatitis while on long-term treatment with 5-aminosalicylic acid.     

Budesonide foam as a new therapeutic principle in distal ulcerative colitis in comparison with mesalazine enema. An open, controlled, randomized and prospective multicenter pilot study

Budesonide is a locally acting steroid with a high first-pass metabolism in the liver and low systemic effects. We performed the first pilot study comparing budesonide foam (1 mg/50 ml b.i.d.) with mesalazine enemas (4 g/60 ml o.d.). 33 patients from 3 centres were enrolled in this open randomized clinical trial. 16 patients got budesonide foam and 17 got mesalazine enemas. The drugs were administered for 4 weeks. Histological index (HI) and endoscopic index (EI) were assessed at day 1 and day 28, clinical activity index (CAI) at day 1, 14 and 28. For patients with left-sided colitis and proctosigmoiditis improvement was defined as decrease in CAI of > or = 2 points. For patients with proctitis improvement was defined as decrease in HI of > or = 1 point. The primary efficacy evaluation was performed with the intention to treat population (n = 32). Improvement was found in 67% of the patients in the budesonide group compared to 71% in the mesalazine group. There was no statistically significant difference between the groups. Adverse events were mild and rare in both groups. Both treatments had no significant influence on plasma cortisol. In this pilot study for distal ulcerative colitis budesonide foam is as safe and effective as mesalazine enema.