美沙拉嗪、柳氮磺胺吡啶对葡聚糖硫酸钠诱导的Balb/c小鼠急性溃疡性结肠炎的治疗和免疫影响

目的：探讨美沙拉嗪和柳氮磺胺吡啶对葡聚糖硫酸钠（DSS）致Balb/c小鼠急性溃疡性结肠炎的作用效果和对急性溃疡性结肠炎免疫功能的影响。方法：Balb/c小鼠给予3.5% DSS水溶液自由饮用7 d建立溃疡性结肠炎模型,通过测定小鼠DAI指数、脏器指数、血清IL-4、结肠组织匀浆液IL-8的表达水平和小鼠体内CD4⁺细胞、CD8⁺细胞、CD4⁺CD25⁺细胞的变化,来评价两种药物对小鼠急性溃疡性结肠炎的作用。结果：给药治疗后,美沙拉嗪组和柳氮磺胺吡啶组的DAI评分和CMDI评分均降低（P<0.01或者P<0.05）,小鼠症状缓解。结肠黏膜充血水肿减轻,且两种药物均能\\有效抑制病灶部位炎细胞的浸润。与模型组相比,美沙拉嗪组和SASP组CD3⁺细胞数增加,CD8⁺细胞数明显上升,CD4⁺CD25⁺细胞占CD4⁺细胞比例增加,血清中IL-4含量显著上升（P<0.01）,组织中IL-8含量显著下降（P<0.01）;而美沙拉嗪组CD4⁺细胞数目略有增加,SASP组CD4⁺细胞数增加比较明显。结论：美沙拉嗪和柳氮磺胺吡啶可减轻DSS诱导的UC小鼠稀便、血便症状;两种药物对UC疾病的治疗可能与提高CD4⁺细胞水平和IL-4含量及上调CD8⁺细胞水平有关。     

Role of pharmacoepidemiology studies in addressing pharmacovigilance questions: a case example of pancreatitis risk among ulcerative colitis patients using mesalazine

Purpose

Well-designed pharmacoepidemiology studies address several limitations of postmarketing spontaneous reports in regard to signal evaluation. This study evaluated a signal of disproportionate reporting of acute pancreatitis cases observed in patients with ulcerative colitis (UC) treated with MMX Multi Matrix System® (MMX®) mesalazine and demonstrated how inherent limitations of postmarketing reports were overcome.

Methods

Adults with UC who were new users of MMX mesalazine or another branded mesalazine (controlled-release, delayed-release, or extended-release mesalazine; balsalazide disodium; olsalazine sodium; sulfasalazine; or sulfasalazine delayed-release) were identified from a large US administrative healthcare claims database. Acute pancreatitis incidence rates were compared between patients on MMX mesalazine versus comparator therapies. Propensity scores were used to match patients on MMX mesalazine with patients on comparator drugs to achieve a balance of baseline patient factors.

Results

Crude incidence rates [95 % confidence interval (CI)] of acute pancreatitis among patients on MMX mesalazine were similar to those of patients on comparator therapies [8.55 (5.54–13.21) vs 10.05 (7.54–13.41) per 1000 person-years]; the resulting incidence rate ratio (IRR) was [0.85 (0.48–1.47)]. Propensity score-matching had little influence on the IRR [0.84 (0.46–1.55)]; nor did further adjustment by demographic characteristics, daily dose, and causes of acute pancreatitis [0.76 (0.41–1.43)].

Conclusion

Findings of no increase in pancreatitis risk with MMX mesalazine demonstrate the value of pharmacoepidemiology studies for evaluating a drug’s postmarket safety profile when confronted with spontaneous reporting data suggestive of a safety issue.     

Rectal and colonic mesalazine concentration in ulcerative colitis: oral vs. oral plus topical treatment

AIM: To measure mucosal concentrations of mesalazine in ulcerative colitis patients treated with oral mesalazine alone, compared to patients treated with both topical and oral mesalazine. METHODS: Twenty-two patients with mild to moderate ulcerative colitis were randomized to receive 2.4 g/day of oral mesalazine (11 patients) or 2.4 g/day oral plus 4 g/day of topical mesalazine (11 patients). After 2 weeks of treatment, endoscopic biopsies specimens were taken from the rectum and in descending colon just distal of the splenic flexure and stored to -80 degrees C for later assay (HPLC). Wilcoxon's rank sum test for unpaired data was used for the statistical analysis. RESULTS: Mucosal levels of mesalazine in the rectum were significantly higher in patients who received oral plus topical treatment than in those who had oral treatment alone (52.1 ng/mg, range: 13.6-122.1 vs. 0.2 ng/mg, range: 0.2-9.7, respectively; P < 0.0001). Similarly, in the descending colon, the mucosal concentrations of mesalazine were significantly higher in patients who had oral plus topical treatment than in those receiving oral treatment alone (46.6 ng/mg, range: 6-112.6 vs. 15.9 ng/mg, range: 2.3-42.4, respectively; P=0.01). CONCLUSIONS: Topical treatment of mesalazine significantly increases mucosal concentrations of mesalazine up to the splenic flexure, supporting the rationale to treat left-sided ulcerative colitis with topical formulations of mesalazine.     

A Large Population-Based Follow-Up Study of Trimethoprim-Sulfamethoxazole,Trimethoprim, and Cephalexin for Uncommon Serious Drug Toxicity

We conducted a population-based 45-day follow-up study of 232,390 people who were prescribed trimethoprim-sulfamethoxazole (TMP-SMZ), 266,951 prescribed trimethoprim alone, and 196,397 prescribed cephalexin, to estimate the risk of serious liver, blood, skin, and renal disorders resulting in referral or hospitalization associated with these drugs. The results were based on information recorded on office computers by selected general practitioners in the United Kingdom, together with a review of clinical records. The risk of clinically important idiopathic liver disease was similar for persons prescribed TMP-SMZ (5.2/100,000) and those prescribed trimethoprim alone (3.8/100,000). The risk for those prescribed cephalexin was somewhat lower (2.0/100,000). Only five patients experienced blood disorders, one of whom was exposed to TMP-SMZ; of seven with erythema multiforme and Stevens-Johnson syndrome, four were exposed to TMP-SMZ. The one case of toxic epidermal necrolysis occurred in a patient who took cephalexin. Finally, only five cases of acute parenchymal renal disease occurred, none likely to be caused by a study drug. We conclude that the risk of the serious diseases studied is small for the three agents, and compares reasonably with the risk for many other antibiotics.     

氧化苦参碱对结肠炎模型大鼠结肠黏膜NOD2与TNF-α的影响

目的研究NOD2在实验性大鼠结肠炎发病机制中的作用,探讨氧化苦参碱对实验性大鼠结肠炎的治疗作用及其机制。方法将32只SD大鼠随机分为4组：对照组、模型组、美沙拉嗪组和氧化苦参碱组,每组8只。除对照组外,其余均采用三硝基苯磺酸造模。氧化苦参碱组给予苦参素注射液肌内注射,美沙拉嗪组给予美沙拉嗪纯化水溶液灌胃,模型组肌内注射等体积0.9%氯化钠注射液,共15 d。观察大鼠结肠黏膜大体形态及组织病理评分,并用免疫组织化学法检测大鼠结肠黏膜NOD2蛋白表达,酶联免疫吸附法检测实验大鼠结肠黏膜α肿瘤坏死因子（TNF α）表达。结果与对照组比较,模型组大鼠结肠黏膜NOD2蛋白、TNF α表达均显著升高（P＜0.01）;与模型组比较,美沙拉嗪组、氧化苦参碱组大鼠结肠黏膜NOD2蛋白、TNF α表达均显著降低（P＜0.01,P＜0.05）。结论结肠黏膜NOD2蛋白过度表达、TNF α分泌增多参与了溃疡性结肠炎的发生发展过程,而氧化苦参碱可以通过抑制NOD2蛋白过度表达、降低TNF α分泌起到减轻结肠黏膜炎症和保护结肠黏膜的作用。     

Use of dexfenfluramine, fenfluramine and phentermine and the risk of stroke

AIMS: To estimate the incidence of newly diagnosed idiopathic stroke among users of fenfluramine, dexfenfluramine and phentermine compared to obese nonusers. METHODS: We conducted a cohort study with nested case-control analysis utilizing data from the General Practice Research Database in the UK. Eight thousand four hundred and twenty-three subjects aged 69 years or less at the start of follow-up were exposed to at least one of the three study drugs and 17 225 similarly obese subjects were not exposed to any of the study drugs. RESULTS: We identified 45 incident cases of idiopathic CVA in this cohort of subjects. The incidence of CVA among all current users of a diet drug was 1.3/1000 person-years (95% CI 0.5, 3.5). The incidence for current fenfluramine users (n=2) was 2.6/1000 person-years (95% CI 0.7, 9.6), for current dexfenfluramine users (n=1) 1.1/1000 person-years (95% CI 0.3, 3.8), and for current phentermine users 0/1000 person-years (95% CI 0.0, 12.9). The incidence in obese nonusers was 0.6/1000 person-years (95% CI 0.4, 0. 9). The adjusted matched odds ratio (OR) for thrombotic stroke from the case-control analysis comparing current use of a diet drug to nonuse was 2.4 (95% CI 0.6, 9.1). There was only one exposed subject among seven who had haemorrhagic stroke. CONCLUSIONS: The incidence of CVA in generally young obese subjects during use of fenfluramine, dexfenfluramine or phentermine is low. Although we found an OR of 2. 4 comparing users of any of the anorexiants with nonusers, this is based on only three exposed cases and the confidence limits are wide. We conclude that our study does not support a substantial increased risk of stroke attributable to the use of fenfluramine, dexfenfluramine or phentermine.     

美沙拉嗪治疗炎症性肠病的疗效及安全性：—全国多中心临床研究

目的：观察一种新型美沙拉嗪控释剂（艾迪莎）治疗炎症性肠病（IBD）的疗效和安全性。并同水杨酸偶碘胺吡啶（SASP）进行比较。方法：本研究是一个随机、多中心、以SASP作为照的临床试验。89例内镜确诊为轻、中度溃疡性结肠炎或克罗恩病急性期（首次发作或复发）的患者随机分成艾迪莎组（n=52)和SASP组（n=37),分别给予艾迪莎或SASP治疗,剂量均为1．0g,qid疗程6周。服药6周后复查内镜。治疗4和6周对药物疗效进行评价,并观察不良反应。结果：在服药4和6周末艾迪莎组患者主观评价为明显好转者分别为52．0％和71．2％,SASP组分别为20．6％和50．0％,2组比较有统计学意义（P＜0．05）。艾迪莎组服药6周症状消失率为57．75,显著高于SASP组（50．0％,P＜0．05）,艾迪莎组6周内镜下显示治愈率为26．9％,显著高于SASP组（2．9％,P＜0．05）。艾迪莎组总体评价为很好者占42．3％,显著高于SASP组（2．9％,P＜0．05）。艾迪莎组和SASP组不良反应的发生率分别为1．9％（1／52）和10．8％（4／37）,2组比较无明显差异（P＞0．05）。结论：艾迪莎是一个治疗IBD的安全有效的药物。     

美沙拉嗪治疗轻中度溃疡性结肠炎患者的肠黏膜愈合率分析

目的:研究不同蒙特利尔分型及Mayo内镜评分的轻中度溃疡性结肠炎患者接受美沙拉嗪为主的治疗方案后的肠黏膜愈合情况以及影响愈合情况的相关因素。方法:收集229例轻中度溃疡性结肠炎且接受美沙拉嗪治疗的患者资料并进行回顾性研究,分析比较不同患者之间肠黏膜愈合率的差异。结果:接受美沙拉嗪治疗后达到黏膜愈合的患者占29.7%(68/161),黏膜愈合率在不同性别患者之间的差异有统计学意义(P<0.05)。不同蒙特利尔分型及Mayo内镜评分的患者之间的黏膜愈合率存在显著性差异(P<0.05)。结论:临床实践中接受美沙拉嗪治疗的轻中度溃疡性结肠炎患者,达到理想的黏膜愈合目标还存在一定差异。患者的性别、肠黏膜的炎症程度与炎症累及的范围对美沙拉嗪疗效的影响具有一定的相关性。     

Risk of stroke with typical and atypical anti-psychotics: a retrospective cohort study including unexposed subjects

The purpose of the study was to investigate the risk of stroke with typical and atypical anti-psychotics in elderly subjects, weighting for a number of known risk factors, including dementia. Data were retrospectively drawn from the primary care setting from the Health Search Database, which stores information on about 1.5% of the total Italian population served by general practitioners. All elderly patients (65+ years) prescribed an anti-psychotic in monotherapy from January 2000 to June 2003 were selected for the study. A cohort of patients not exposed to anti-psychotics was taken from the same database. Subjects who had previously had a stroke were excluded. The main outcome measure was the incidence of first-ever stroke during exposure to an anti-psychotic.The sample included non-users (69,939), users of atypicals (599), butyrophenones (749), phenotiazines (907) and substituted benzamides (1,968). The crude incidence of stroke in subjects not exposed to anti-psychotics was 12.0/1000 person-years. Risk was significantly higher for those on butyrophenones (47.1/1000), phenotiazines (72.7/1000) and in the atypical anti-psychotic group (47.4/1000). Substituted benzamides had an almost significant higher risk (25.0/1000). Cox regression modelling, weighting for demographic and clinical variables with non-users as the reference group, showed that the risk for stroke was 5.79 times for phenotiazines, 3.55 times for butyrophenones, and 2.46 times for atypicals. Clinicians should be cautious in prescribing phenotiazines and butyrophenones in elderly patients, since the risk for stroke would seem comparable or even greater than with atypicals.     

The risk of severe depression, psychosis or panic attacks with prophylactic antimalarials.

INTRODUCTION/OBJECTIVE: Experimental and observational studies have linked mefloquine use to an increased risk of developing neuropsychiatric adverse effects such as depression or psychoses. Most of these reports relied on interview-based information from travellers. We conducted a population-based observational study using a database of medical records to quantify and compare the risk of psychiatric disorders during or after use of mefloquine with the risk during use of proguanil and/or chloroquine, or doxycycline. STUDY DESIGN/METHODS: The study population was drawn from the large UK-based General Practice Research Database (GPRD). Subjects were aged from 17-79 years and were exposed to mefloquine, proguanil, chloroquine or doxycycline (or a combination of these drugs) at some time between 1990 and 1999. We performed a person-time and a nested case-control analysis to assess the risk of developing a first-time diagnosis of depression, psychosis or panic attack during or after use of these antimalarial drugs. RESULTS: Within the study population of 35 370 subjects (45.2% males), we identified 580 subjects with a first-time diagnosis of depression (n = 505), psychosis (n = 16) or panic attack (n = 57) and two subjects committed suicide. The incidence rates of first-time diagnoses of depression during current use of mefloquine, proguanil and/or chloroquine, or doxycycline, adjusted for age, gender and calendar year, were 6.9 (95% CI 4.5-10.6), 7.6 (95% CI 5.5-10.5) and 9.5 (95% CI 3.7-24.1)/1000 person-years, respectively. The incidence rates of psychosis or panic attacks during current mefloquine exposure were 1.0/1000 person-years (95% CI 0.3-2.9) and 3.0/1000 person-years (95% CI 1.6-5.7), respectively, approximately 2-fold higher (statistically nonsignificant) than during current use of proguanil and/or chloroquine, or doxycycline. The nested case-control analysis encompassed 505 cases with depression and 3026 controls, 16 cases with psychosis and 96 controls, and 57 cases with a panic attack and 342 controls. Current use of mefloquine was not associated with an elevated risk of developing depression. In a comparison between patients currently using mefloquine with all past users of antimalarials combined, the risk estimate was elevated for current users of mefloquine for both psychosis (odds ratio [OR] 8.0, 95% CI 1.0-62.7; p < 0.05) and panic attacks (OR 2.7, 95% CI 1.1-6.5; p < 0.05). CONCLUSION: The absolute risk of developing psychosis or panic attack appears low with all the antimalarials tested. No evidence was found in this large observational study that mefloquine use increased the risk of first-time diagnosis of depression when compared with the use of other antimalarials investigated in this study.     

Comparison of the effect of mesalazine and sulfasalazine on laboratory parameters: a retrospective observational study

Purpose

Mesalazine and sulfasalazine are commonly used drugs for the treatment of inflammatory bowel disease. However, there have been few reports with a strict statistical analysis comparing the effects of mesalazine and sulfasalazine on laboratory test results. Therefore, we designed a retrospective cohort study to investigate whether or not differences in clinical laboratory parameters exist between mesalazine and sulfasalazine users.

Methods

We used data from the Clinical Data Warehouse of Nihon University School of Medicine to identify cohorts of new mesalazine users (n?=?303) and sulfasalazine users (n?=?67). We used a multivariate regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between mesalazine and sulfasalazine users, and compared serum levels of creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and hematological parameters including red and white blood cell counts and platelet count.

Results

After adjustment, in sulfasalazine users, the mean values for all tests showed no significant change between baseline and during the exposure period. In contrast, in mesalazine users, the mean WBC and platelet counts during the exposure period were significantly lower than those at baseline. Furthermore, mean serum urea nitrogen level during the exposure period was significantly higher than that at baseline. In terms of mean changes in laboratory test values during the exposure period compared with baseline, the reduction of platelet count in mesalazine users was significant in comparison to that in sulfasalazine users.

Conclusion

Our findings suggested that the hematological adverse effects of mesalazine treatment might be greater than those of sulfasalazine treatment.     

The Risk of Myocardial Infarction Associated with Antihypertensive Drug Treatment in Persons with Uncomplicated Essential Hypertension

We conducted a case-control study based on computer-recorded information accrued in the United Kingdom General Practice Research Database to assess and compare the relation between different antihypertensive drug therapies and myocardial infarction in patients with no known clinical or laboratory risk factors for myocardial infarction other than hypertension. Cases were treated hypertensive patients with no other known risk factors who developed a first acute myocardial infarction between January 1, 1993, and October 31, 1994. They were ascertained from a review of the clinical record together with a questionnaire filled out by the attending general practitioner. Controls were matched to each case for age, sex, general practice, and index date. Antihypertensive therapy was derived from the computerized patient record. The study consisted of 210 cases and 793 controls. Compared with users of β-blockers alone, the adjusted relative risk (RR) estimates for all other treatment regimens were close to 1.0. A comparison of users of calcium channel blockers alone with users of β-blockers alone yielded a RR estimate of 0.9 (95% CI 0.5, 1.7). We conclude that the risk of acute myocardial infarction in otherwise healthy, treated hypertensive patients is not materially associated with the particular drug they receive.     

High prevalence of substance use disorders among adolescents who use marijuana and inhalants

BACKGROUND: We examined the association between the use of inhalants, marijuana, and other drugs and recent DSM-IV substance use disorders among adolescents aged 12-17 years. METHODS: Data were drawn from 2000 to 2001 National Household Surveys on Drug Abuse. Adolescents aged 12-17 years who reported having ever used an illicit drug in their lifetime were categorized into four mutually exclusive groups: inhalant users (16%), marijuana users (53%), inhalant and marijuana users (16%), and other drug users (15%). Logistic regression models were used to estimate associations with recent substance use diagnoses among lifetime adolescent drug users (N=10,180). RESULTS: We found that 31% of lifetime drug users reported having never used marijuana. One half of these atypical drug users were predominantly nonmedical users of pain relievers. Adolescents who used inhalants or other drugs but not marijuana were least likely to report multidrug use. Adolescents who reported using both inhalants and marijuana were most likely to use three or more classes of drugs (73%) and to receive a diagnosis of past year alcohol (35%) and drug (39%) abuse or dependence. CONCLUSIONS: Our study findings suggest that among lifetime adolescent drug users, those who use both inhalants and marijuana are at very high risk for alcohol and drug use disorders.     

Gastro-intestinal problems and concomitant medication in NSAID users: additional findings from a questionnaire-based survey in Italy

Background In a previous questionnaire-based survey, we found extensive use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with risk factors for serious gastrointestinal complications. Aim This study focused on the use of NSAIDs in subjects who reported either (a) pre-existing disorders which would have required caution in using NSAIDs (e.g. dyspepsia/heartburn or peptic ulcer) or (b) co-medication with drugs having a high risk of interacting with NSAIDs. Methods Between March and September 2002, 65 general practitioners (GPs) submitted a validated self-administered questionnaire on health status and drug use to 3,250 subjects (age ≥18 years, stratified by sex and age). The questionnaire was divided into three parts: (1) sociodemographic information, (2) symptoms/illnesses (in the previous 6 months) and (3) drugs taken during the previous week. Results Of the 2,738 subjects who filled in the questionnaire (84% of responders), 633 (23%) used NSAIDs and, among them, 114 (18%) were chronic users. Among the subjects reporting dyspepsia/heartburn or ulcer (n=909 of 2,738), 24% were occasional NSAID users and 6% chronic users. Of the chronic NSAID users reporting gastrointestinal symptoms, 35% also used a drug for acid-related disorders, but only 14% used daily a proton pump inhibitor (PPI). One hundred six subjects used concomitantly more than one NSAID. Eighteen percent of the subjects using corticosteroids also reported NSAID use; similar proportions were seen in subjects using selective serotonin reuptake inhibitor (SSRI) antidepressants or calcium channel blockers, whereas 6% of the subjects with oral anticoagulants used NSAIDs. Conclusions Our study shows that NSAIDs are frequently used in patients with upper gastrointestinal complaints or in combination with potentially interacting medications. Adverse effects and untoward drug interactions should be monitored in patients treated with NSAIDs in order to minimise their occurrence.     

Risk of serious morbidity associated with hydralazine versus methyldopa treatment in hypertensive patients

Summary The medical records of patients presenting to the Hammersmith Hospital hypertension clinic between 1971 and 1981 were examined to determine presenting clinical data, treatment regimes, and both cardiovascular and non cardiovascular mortality and morbidity.When compared with 1004 patients receiving treatment other than hydralazine 310 patients on hydralazine had a significantly higher risk of developing renal disease (RR=2.71) in men, and severe weight loss in women (RR = 3.06). Renal disease risk also tended to be high in women on hydralazine (RR = 1.95) compared with all other treatments, but this was not statistically significant and could be explained by poorer renal function and significantly higher untreated blood pressure in the hydralazine treated group at presentation.The 422 patients who were treated with methyldopa but not hydralazine had similar risk factors for cardiovascular disease compared with a group of 167 who received hydralazine but not methyldopa. Comparisons of event rates failed to find significant differences in morbidity or mortality between these two groups. The age adjusted male mortality was 14/1000 patient years on hydralazine and 12/1000 on methyldopa and 13/1000 and 6/1000 years for women respectively. There was no evidence of an increased risk of either renal disease (RR=0.3 in men, RR=0.3 in women) on hydralazine or weight loss (RR=0.7 in men, RR=1.6 in women), with similar presenting data.Systemic lupus erythematosus was a rare complication (2 of 314) of treatment with hydralazine.     

Liver Disorders in Patients Receiving Chlorpromazine or Isoniazid

Based on information derived from computers and clinical records obtained from general practitioners in the United Kingdom, we estimated the frequency of liver toxicity associated with two known hepatotoxins, chlorpromazine and isoniazid. Among the cohort of 10,502 users of chlorpromazine, 14 had illnesses compatible with drug-induced liver disease, a frequency of 1.3/1000 users (95% CI 0.8, 2.2). Four presumed cases of the disorder occurred among 921 users of isoniazid, for a frequency of 4/1000 users (95% CI 1.7, 11.1). This study provides population-based quantification of the frequency of liver disorders associated with the use of these two agents.     

美沙拉嗪口服联合中药灌肠治疗溃疡性结肠炎临床观察

目的观察美沙拉嗪口服联合中药灌肠治疗溃疡性结肠炎的临床疗效。方法 65例患者随机分为治疗组35例,用美沙拉嗪口服联合中药保留灌肠,对照组30例用SASP口服及保留灌肠,观察两组临床症状、结肠黏膜的改善情况及不良反应。结果治疗组和对照组的总有效率分别为94.3%和73.3%,两组临床疗效比较有显著性差异（P〈0.05）,治疗组症状及结肠黏膜的改善情况优于对照组（P〈0.05）,治疗组与对照组的不良反应比较有高度显著性差异（P〈0.01）。结论美沙拉嗪口服联合中药保留灌肠治疗溃疡性结肠炎安全有效。     

Systematic review: the potential influence of mesalazine formulation on maintenance of remission in Crohn's disease

AIM: To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn's disease remission. METHODS: A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn's disease activity index >150, or an increase in baseline by at least 60-100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated. RESULTS: Treatment with pH 7-dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12-0.65; P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17-0.85; P = 0.0113). However, treatment with controlled-release mesalazine and pH 6-dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6-dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and 4.4%, respectively, for pH 6-dependent mesalazine. CONCLUSION: Further trials of pH 7-dependent mesalazine formulations are warranted in the maintenance of remission in Crohn's disease.