Divergent patterns of total and cancer mortality in ulcerative colitis and Crohn's disease patients: the Florence IBD study 1978-2001.

BACKGROUND AND AIMS: Two divergent patterns of mortality for smoking related diseases in ulcerative colitis and Crohn's disease patients were suggested in a previous population based study in Florence, Italy. Long term follow up (median 15 years) was completed to re-evaluate mortality in this Mediterranean cohort. PATIENTS AND METHODS: Overall, 920 patients with inflammatory bowel disease were followed until December 2001 or death, with seven patients (0.8%) lost to follow up. A total of 14 040 person years were available for analysis; 118 deaths were observed (81/689 in ulcerative colitis and 37/231 in Crohn's disease). Expected deaths were estimated using age, sex, and calendar specific national and local mortality rates; standardised mortality ratios (SMR) and 95% confidence interval (CI) were calculated. RESULTS: Among Crohn's disease patients, mortality was strongly increased for gastrointestinal diseases (SMR 4.49 (95% CI 1.80-9.25)), all cancers (SMR 2.10 (95% CI 1.22-3.36)), and lung cancer (SMR 4.00 (95% CI 1.60-8.24)), leading to a significant 50% excess total mortality. Ulcerative colitis patients showed a significantly reduced total mortality because of lower cardiovascular (SMR 0.67 (95% CI 0.45-0.95)) and lung cancer (SMR 0.32 (95% CI 0.07-0.95)) mortality. No significant excess for colorectal cancer mortality was evident in this extended follow up. CONCLUSIONS: These clearly divergent patterns of mortality correlate with documented differences in smoking habits between Crohn's disease and ulcerative colitis patients. Family doctors and gastroenterologists should consider stopping cigarette smoking a specific priority for Crohn's disease patients; the latter should be offered free participation in structured programmes for smoking cessation, with the aim of reducing smoking related excess mortality. Overall, no evidence of an increased mortality for large bowel cancer emerged in this series.

Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study.

AIM: To explore the efficacy and safety of the topically acting steroid beclometasone dipropionate (BDP) in an oral controlled release formulation in the treatment of extensive or left-sided ulcerative colitis. METHODS: In a multicentre, randomised, parallel-group, single-blind study, patients with active mild to moderate ulcerative colitis were randomised to a 4-week treatment with BDP 5 mg/day o.d. vs. 5-ASA 0.8 g t.d.s. The primary efficacy variable was the decrease of Disease Activity Index (DAI) (clinical symptoms and endoscopic appearance of mucosa). Safety was evaluated by monitoring adverse events, vital signs, haematochemical parameters and adrenal function. RESULTS: One hundred and seventy-seven patients were enrolled and randomly treated with BDP (n = 90) or 5-ASA (n = 87). Mean DAI score decreased in both treatments groups (P < 0.0001 vs. baseline for both groups). Clinical remission was achieved in 63.0% of patients in the BDP group vs. 62.5% in the 5-ASA group. A significant DAI score improvement (P < 0.05) in favour of BDP was observed in patients with extensive disease. Both treatments were well tolerated. Mean plasma cortisol levels were significantly reduced vs. baseline in BDP recipients, but without signs of pituitary-adrenal function depletion. CONCLUSION: Oral BDP gave an overall treatment result in patients with active ulcerative colitis without signs of systemic side-effects.

Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial.

BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.

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.

Suppressive effect of 1,25-dihydroxyvitamin D3 and its analogues EB 1089 and KH 1060 on T lymphocyte proliferation in active ulcerative colitis.

This study examined the effect exerted by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and two vitamin D analogues, EB 1089 and KH 1060, on the proliferation of T lymphocytes obtained from ulcerative colitis (UC) patients and healthy controls. The proliferative response of T lymphocytes to phytohaemagglutinin treatment was first analyzed on days three, five, and seven of culture. Cell proliferation was significantly lower in UC patients than that observed in healthy controls. The highest proliferation value, in either controls or patients, was registered on day five of culture. On day seven, a decrease in proliferation occurred, less evident in patients with respect to controls, whereas on day three, controls and patients showed the same proliferation value. The response of T lymphocytes of either healthy controls or UC patients to 1,25(OH)2D3, EB 1089, or KH 1060 was then investigated, treating the cells for three, five, and seven days with 10 nM vitamin D derivatives. In the presence of these compounds, cell proliferation was significantly inhibited in both groups, but on day seven, the inhibition of lymphocyte proliferation was remarkable in controls, whereas in patients it was similar to that registered on day five. The highest inhibition values were always obtained in the presence of KH 1060, and the time dependence was continuous in controls, but in the presence of EB 1089 only in patients. T lymphocytes prepared from healthy controls and UC patients were then cultured for five days in the presence of vitamin D derivatives at three different concentrations (0.1, 1, and 10 nM). In the two groups, a dose-dependent inhibition was registered in the presence of 1,25(OH)2D3 or EB 1089, while the inhibition of proliferation exerted by KH 1060 was not dose-dependent. The results obtained suggest an option for the use of the two non-hypercalcemic vitamin D analogues in the therapy of UC patients, perhaps in association with other immunosuppressive drugs.

Hodgkin's disease risk is increased in patients with ulcerative colitis.

BACKGROUND & AIMS: All patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) residing in Florence, Italy, in 1978-1992 were identified and included in a population-based study of cancer risk evaluation. METHODS: A total of 920 patients were followed up (median, 11 years), and 64 newly diagnosed malignancies were identified by linkage to the local cancer registry. Expected cases were calculated on the basis of age- and sex-specific cancer incidence rates to estimate relative risks in comparison with the general population. RESULTS: Overall, cancer incidence rates were not increased. A significant excess risk of Hodgkin's disease was observed among patients with UC (standardized incidence ratio, 9.3; 95% confidence interval [CI], 2.5-23.8). Respiratory tract cancers were significantly reduced to one fourth of the expected rate in patients with UC, but tended to be increased among patients with CD, who had a 50% higher risk of cancer at all sites. Only a nonsignificant, modestly increased risk of colorectal cancer was observed. CONCLUSIONS: A strongly increased risk of Hodgkin's disease was evident in this first cancer follow-up of a representative series of patients with UC in a Mediterranean country. Two divergent risk patterns of respiratory tract cancers, possibly explained by differences in smoking habits, emerged in the 2 inflammatory bowel diseases.

A new mesalazine gel enema in the treatment of left-sided ulcerative colitis: a randomized controlled multicentre trial.

BACKGROUND: A new mesalazine rectal gel preparation (without propellant gas) has been recently developed to improve topical treatment in distal ulcerative colitis. AIM: To evaluate the efficacy, safety and patient tolerability of mesalazine gel enema compared with mesalazine foam enema in the treatment of patients with acute left-sided ulcerative colitis. METHODS: In a randomized multicentre investigator-blind parallel group trial, 103 patients with mild to moderate left-sided colitis or proctosigmoiditis were randomly allocated to mesalazine 2 g gel enema (n = 50 evaluable patients) and mesalazine 2 g foam enema (n = 53 evaluable patients) for 4 weeks. Clinical symptoms, endoscopic and histological findings were assessed at entry, 2 and 4 weeks. Patients' evaluation of treatment tolerability and acceptability was assessed at 2 and 4 weeks. RESULTS: After 4 weeks of treatment, clinical remission was achieved by 76% of mesalazine gel enema-treated patients and 69% of patients treated with mesalazine foam enema (P = 0.608). Endoscopic remission rates at week 4 were 51 and 52% for the mesalazine gel and foam enemas, respectively (P = 0.925). Histological remission was achieved by 30% of patients in both groups. Patients reported that the new mesalazine gel preparation was significantly better tolerated than the foam enema. Patients in the foam group had significantly more difficulty in retention (25% vs. 6%, P < 0.05), abdominal bloating (50% vs. 26%, P < 0.005) and discomfort during administration (48% vs. 26%, P < 0.05). CONCLUSION: The new mesalazine gel enema is efficacious and significantly better tolerated than the mesalazine foam enema.

Beclomethasone dipropionate enemas versus prednisolone sodium phosphate enemas in the treatment of distal ulcerative colitis.

AIM: To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60 mL enema (PP) once daily in patients with active distal ulcerative colitis. METHODS: One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks. RESULTS: Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic-pituitary-adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups. CONCLUSIONS: It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group.

OBJECTIVES: A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis. METHODS: From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (< or = 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurrence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features. RESULTS: The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0-21) in the mesalazine b.i.d. group, 32% (95% CI: 16-49) in the mesalazine u.i.d. group, and 47% (95% CI: 29-65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up. CONCLUSIONS: The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.

General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence Study.

BACKGROUND: A population based epidemiological study identified all the patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) resident in the Florence area in the period 1978-1992. AIMS: To assess the mortality of unselected patients with inflammatory bowel disease (IBD) in a Mediterranean country. METHODS: Overall, 920 patients (689 UC and 231 CD) were followed until death or end of follow up (31 December 1996). Information on vital status was available for all except eight patients (0.9%); 70 deaths were identified (23 in patients with CD and 47 in patients with UC). Expected deaths were estimated on the basis of five year age group, gender, and calendar year national mortality rates. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated. RESULTS: General mortality was significantly lower than expected in UC (SMR 0.6; 95% confidence interval 0.4 to 0.8), due to a reduced number of cardiovascular and, possibly, smoking related deaths. Cancers of the respiratory tract were significantly reduced in UC but tended to be increased in patients with CD. These latter patients had not only an increased cancer mortality but also a 40% increased risk of dying for all causes already evident in the first five year follow up period and persisting thereafter. In contrast, in patients with UC, SMRs were initially very low but tended to increase steadily over the follow up period. Gastrointestinal deaths were particularly increased in patients with CD, but only moderately in those with UC. Overall, there was some evidence of a twofold increased mortality for colorectal cancer, the risk being highest for rectal cancers in patients with UC. A non-significant excess of deaths due to haemolymphopoietic malignancies and suicides was also observed. CONCLUSIONS: This study, the first in a Mediterranean country, supports the existence of two divergent mortality patterns for patients with UC and CD, possibly explained by differences in smoking habits and by a greater severity of CD.

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study.

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.

Spondyloarthritis in patients with ulcerative colitis.

BACKGROUND: Extraintestinal manifestations can complicate the course of ulcerative colitis and can influence the prognosis. AIMS: Sixty-eight patients of the metropolitan area of Florence with ulcerative colitis in clinical and endoscopic remission were evaluated to establish the presence of spondyloarthritis. PATIENTS AND METHODS: Each patient was studied through clinical and radiological evaluations to assess the presence of joint involvement. RESULTS: We found signs of spondyloarthritis in 19 patients (27.9%). Four of them had a classic ankylosing spondylitis (5.8%) and in 3 of them the aplotype HLA B27 was present. Sacroileitis was found in 9 (13.2%) patients (monolateral in 5 cases and bilateral in 4). Six patients (8.8%) showed an unclassifiable form of arthritis, fulfilling the Amor criteria. In 13 of 19 patients with spondyloarthritis, we found a pancolic extension of disease (68.4%). CONCLUSIONS: The results obtained from our series of ulcerative colitis patients reveal a lower proportion of cases of spondyloarthritis than that found in other Italian studies. We are planning further investigations on a larger population to better assess the prevalence of spondyloarthritis in ulcerative colitis patients.

A population-based study of inflammatory bowel disease in Florence over 15 years (1978-92).

BACKGROUND: In the group of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are considered to be more frequent in Western countries and in areas with a high socioeconomic development but relatively infrequent in southern Europe. Sporadic reports have indicated a lower incidence and a milder course of the disease in Mediterranean countries. Although conclusive data on this point are still lacking, recent reports suggest an increase in both incidence and prevalence rates. METHODS: The incidence of UC and CD during the period January 1978 to December 1992 and their prevalence on 31 December 1992 were estimated in the 15-year-old population of the metropolitan area of Florence. Clinical, demographic, and follow-up information was collected for all identified IBD patients. RESULTS: A total of 796 residents (345 females and 454 males) were newly diagnosed as having IBD during the study period. Of these 593 had UC and 203 CD. The age-standardized incidence rates, calculated for each of five 3-year consecutive periods, rose from 3.8 (in 1978-80) to 9.6 per 100,000 person-years (in 1990-92) for UC and from 1.9 (in 1978-80) to 3.4 (in 1990-92) for CD. Both trends were statistically significant. The prevalence estimated on 31 December 1992 was 121.0 and 40.0 per 100,000 inhabitants for UC and CD, respectively. CONCLUSIONS: Our results confirm that IBD incidence rates and prevalence in this area of central Italy are currently comparable with those reported in northern Europe. These data are necessary for planning adequate health care services for IBD patients.

Defined-formula diets versus steroids in the treatment of active Crohn's disease: a meta-analysis.

BACKGROUND: To compare the effectiveness of defined-formula diets versus steroids for the treatment of active Crohn's disease, we conducted a meta-analysis of the published clinical trials. METHODS: Standard techniques for literature search were used to identify the pertinent trials. All studies included in our meta-analysis (n = 7) were aimed at comparing defined-formula diets versus steroids, using a randomized design. The patient-specific end-point of the meta-analysis was the occurrence of a treatment failure. RESULTS: Our meta-analysis indicated that steroids are more effective than defined-formula diets for inducing remission in active Crohn's disease. In fact, the relative risk of treatment failure (RTF) was significantly lower in the steroid group than in the diet group (risk values for patients given steroids compared with patients given diet: a) method of Mantel-Haenszel: RTF = 0.35; 95% confidence interval, 0.23-0.53; p < 0.001; b) method of Der Simonian & Laird: RTF = 0.43; 95% confidence interval, <0-0.94; p = 0.03). A separate analysis was carried out in which only the subgroup of patients who were not intolerant to diet were evaluated; this analysis also showed a superiority of steroids over diet. CONCLUSIONS: The data examined in this meta-analysis do not support the use of diets as primary treatment for acute exacerbations of Crohn's disease in adults.

Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group.

BACKGROUND/AIMS: Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery. METHODS: In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed. RESULTS: Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1. CONCLUSIONS: This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.

Intermittent versus continuous 5-aminosalicylic acid treatment for maintaining remission in ulcerative colitis.

We performed a 12-month clinical trial to compare the relative effectiveness of an intermittent 5-ASA regimen and a continuous 5-ASA regimen for the maintenance treatment of patients with ulcerative colitis in remission. Fifty patients with ulcerative colitis in remission for a minimum period of 1 month participated in the study. Twenty five patients received an intermittent treatment with 5-ASA tablets (2.4 g for the first week of each month) and 25 received a continuous treatment with tablets (1.6 g each day). Patients were assessed clinically every two months and endoscopically every 6 months. Our results show that the two treatments were equally effective. The relapse-free rates at 12 months were 71% in patients receiving the intermittent treatment and 66% in patients given the continuous treatment. This difference is not statically significant. Further studies are needed to assess whether the intermittent regimen can be an alternative to life-long treatment in patients who have maintained remission for a long period of time.

Effectiveness of 5-aminosalicylic acid for maintaining remission in patients with Crohn's disease: a meta-analysis.

OBJECTIVES: We conducted a meta-analysis of the published randomized clinical trials to evaluate the effectiveness of 5-aminosalicylic acid (5-ASA) for maintaining remission in inactive Crohn's disease. METHODS: The trials were identified by standard computerized techniques for literature search. All studies included in the meta-analysis were aimed at evaluating the effectiveness of 5-ASA in comparison with a control group receiving either no treatment or placebo. RESULTS: Our meta-analysis of five clinical trials published as full-length articles indicates that 5-ASA significantly reduces the relapse frequency in patients with inactive Crohn's disease [odds-ratios (95% CI): 0.56 (0.37-0.84) at 6 months, 0.47 (0.33-0.67) at 12 months, 0.53 (0.38-0.73) at 24 months]. The pooled relapse-free rates in the treatment group were 91% at 6 months, 84% at 12 months, and 72% at 24 months; the corresponding rates in the control group were 77%, 60%, and 52%. A second meta-analysis, conducted using the additional information deriving from four randomized trials published as abstracts, gave essentially the same results. CONCLUSIONS: Whereas our meta-analysis shows that the effectiveness of 5-ASA is statistically significant, a simple pharmacoeconomic assessment indicates that the cost for preventing each relapse can lie between $4,000 and $10,000. This cost compares favorably with the average cost for treating a relapse.

5-Aminosalicylic acid in pregnancy: clinical report.

Ulcerative colitis (UC) is a disease condition which typically affects young people; pregnancy is therefore frequent in women with this disease. 5-aminosalicylic acid (5-ASA) is known to be efficacious in maintaining remission of UC, but its safety in pregnancy has not yet been established. In the present study, the safety of 5-ASA was assessed in 16 women with UC (mean age: 31 years, range 25-35) who had a total of 19 pregnancies over the period from 1988 to 1992. All the patients were in clinical remission of UC at the beginning of pregnancy and were receiving a regular maintenance therapy with 5-ASA (ASACOL tablets, 1.2 g/day). During pregnancy, 4 women had a clinical relapse requiring treatment with higher doses of 5-ASA and, in some cases, with steroids. Our observations confirm that the treatment with 5-ASA does not affect the course of pregnancy nor does it damage the fetus, but it can protect from recurrences of UC.

Oral mesalazine (5-aminosalicylic acid; Asacol) for the prevention of post-operative recurrence of Crohn's disease. Gruppo Italiano per lo Studio del Colon e del Retto (GISC).

METHODS: A multicentre randomized controlled trial was conducted to evaluate the efficacy of oral mesalazine (5-aminosalicylic acid) for the prevention of post-operative recurrence in 110 patients operated on for Crohn's disease by first intestinal resection. Patients were randomly allocated to receive 2.4 g/day of mesalazine, or no treatment at all. The protocol included colonoscopy with ileoscopy at 6 months and yearly thereafter. Recurrence was defined on the basis of endoscopic criteria and classified as mild or severe. RESULTS: The demographic and pre-trial characteristics were very similar in the two groups of patients. The cumulative proportion of recurrence at 6, 12 and 24 months was significantly lower in the mesalazine group than in untreated group (P = 0.002). At 24 months the cumulative proportions of endoscopic recurrence were 0.52 +/- 0.12 (+/- S.E.M.) and 0.85 (+/- 0.07), respectively. At the same time the cumulative proportions of symptomatic recurrence were 0.18 +/- 0.09 and 0.41 +/- 0.09 (P = 0.006). The cumulative proportions of the severe recurrence was also significantly lower in the mesalazine group (0.17 +/- 0.09 vs. 0.38 +/- 0.09; P = 0.021). CONCLUSIONS: The preliminary results of this study show that administration of oral mesalazine soon after surgery is effective in preventing post-operative endoscopic recurrence in Crohn's disease over a 2-year period. It is estimated that this treatment prevents 39% of all recurrences and 55% of the severe recurrences.