Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis. A randomized, double-blind multicenter trial. Danish 5-ASA Group. 5-Aminosalicylic acid as enemas or suppositories in distal ulcerative colitis? Short-chain fatty acid enemas: a cost-effective alternative in the treatment of nonspecific proctosigmoiditis. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. A double-blind clinical trial to compare the effects of 4-aminosalicylic acid to 5-aminosalicylic acid in topical treatment of ulcerative colitis. A comparison of mesalamine suspension enema and oral sulfasalazine for treatment of active distal ulcerative colitis in adults. A new mesalazine foam enema (Claversal Foam) compared with a standard liquid enema in patients with active distal ulcerative colitis. Mesalazine suppositories versus hydrocortisone foam in patients with distal ulcerative colitis. A comparison of the efficacy and practicality of two topical treatment regimens. Mesalamine foam enema versus mesalamine liquid enema in active left-sided ulcerative colitis. 5-Aminosalicylic acid enemas in refractory distal ulcerative colitis: a randomized, controlled trial. Low Pentasa dosage versus hydrocortisone in the topical treatment of active ulcerative colitis: a randomized, double-blind study. Topical treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine: a single-blind randomized controlled trial. Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis. Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis. Sulphasalazine retention enemas in ulcerative colitis: a double-blind trial. Comparison of 5-aminosalicylic acid (3 g) and prednisolone phosphate sodium enemas (30 mg) in the treatment of distal ulcerative colitis. A prospective, randomized, double-blind trial. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. A defence of the small clinical trial: evaluation of three gastroenterological studies. Clinical trial: randomized-controlled clinical study comparing the efficacy and safety of a low-volume vs. a high-volume mesalazine foam in active distal ulcerative colitis. Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis. A multicenter comparative trial with 5-ASA enema. Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: a double-blind, randomized, placebo-controlled study. Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial. Beclomethasone dipropionate versus mesalazine in distal ulcerative colitis: a multicenter, randomized, double-blind study. A new mesalazine gel enema in the treatment of left-sided ulcerative colitis: a randomized controlled multicentre trial. Comparison of oral with rectal mesalazine in the treatment of ulcerative proctitis. Comparison of mesalazine suppositories in proctitis and distal proctosigmoiditis. A new oral delivery system for 5-ASA: preliminary clinical findings for MMx. Mesalazine foam (Salofalk foam) in the treatment of active distal ulcerative colitis. A comparative trial vs Salofalk enema. The SAF-3 study group. A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis. Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using 99mTc-labeled 5-ASA suppositories. Beclomethasone dipropionate (3 mg) versus 5-aminosalicylic acid (2 g) versus the combination of both (3 mg/2 g) as retention enemas in active ulcerative proctitis. Mesalazine (5-aminosalicylic acid) suppositories in the treatment of ulcerative proctitis or distal proctosigmoiditis. A randomized controlled trial. Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial.
The therapeutic efficacy of a slightly acidic, buffered suspension of 1000 mg 5-aminosalicylic acid (Pentasa) was compared with that of 25 mg prednisolone following daily rectal administration to outpatients with mild to moderate proctosigmoiditis. The study was carried out as a randomized, double-blind trial in seven gastroenterological departments. A total of 123 patients were included of whom 114 completed the study (53 5-aminosalicylic acid, 61 prednisolone). The patient population was representative for the disease as it ordinarily appears in medical outpatient clinics. After 14 days, patients in total remission discontinued the treatment, while the rest were treated for another two-week period. Improvement or remission was seen in 77% of the 5-aminosalicylic acid-treated patients and in 72% of the prednisolone-treated patients (P greater than 0.05). More than half the patients requiring prolonged treatment benefited from it, which points to an advantage of extended therapy. Side effects were few and mild. It is concluded that the applied suspension of 5-aminosalicylic acid is at least as efficient as prednisolone for topical treatment of patients with slightly to moderately active proctosigmoiditis. Thirty-nine patients with documented active distal proctitis (less than 20 cm) received either 5-aminosalicylic acid (5-ASA) enemas (2 g in 100 ml) or suppositories 1 g b.i.d., in a controlled study. Twenty patients received enemas, while 19 patients received suppositories, for 30 days. No difference could be observed in terms of efficacy; however, it was the patients' opinion that treatment with suppositories was easier than that with enemas (p less than 0.01). The purpose of this study was to perform a randomized, prospective comparison of corticosteroid enemas (CS--100 mg of hydrocortisone/60 cc P.R. q.h.s.; n = 12), mesalamine enemas (5-ASA--4 g/60 cc P.R. q.h.s.; n = 19), and short-chain fatty acid enemas (SCFA--60 cc P.R. b.i.d.; n = 14) for the treatment of proctosigmoiditis. Patients presenting to the Ferguson Clinic with the diagnosis of idiopathic proctosigmoiditis were evaluated for age, sex, prior history of proctitis, duration of symptoms prior to presentation, endoscopic scoring, and mucosal biopsies. Clinical evaluation was performed at two-week intervals for six weeks, with repeat biopsies taken at six weeks. There was no significant difference with respect to age, male/female ratio, past history of proctosigmoiditis, length of colorectum involved at the time of initial presentation, symptom resolution, and endoscopic and histologic improvement among the three treatment groups. Recovery occurred in a similar proportion in each of the three groups: CS, 10/12; 5-ASA, 17/19; and SCFA, 12/14. The cost of six weeks of treatment was: CS, $71.82; 5-ASA, $347.28; and SCFA, $31.50. This study indicates that SCFA enemas are equally efficacious to CS or 5-ASA enemas for the treatment of proctosigmoiditis at a significant cost savings. The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon. Seventy-six patients received active medication and 77 received a placebo. There were 20 dropouts (6 in the active group and 14 in the placebo group) during the study because of insufficient efficacy. After 6 wk of therapy, 48 of the 76 patients (63%) receiving 5-aminosalicylic acid were considered to be "much improved" by the study physician compared to 22 of the 77 patients (29%) on placebo (p = 0.001). A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy. Mean disease activity index declined 55% for patients on 5-aminosalicylic acid and 24% for patients on placebo (p = 0.0001). Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20-40 cm from the anus. Response was not affected by concurrent sulfasalazine, but patients requiring concurrent oral steroids had a diminished response. Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation. 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon. 5-Aminosalicylic acid (5-ASA) is the active component of Salazopyrin and induces a prompt and excellent improvement, when administered as high dosage enema, in patients suffering from active ulcerative colitis. However, the high instability of this metabolite makes its large use difficult. We aimed at finding a more stable preparation and therefore wondered whether another similar molecule, i.e. 4-aminosalicylic acid (4-ASA, generally known as p-aminosalicylic acid, PAS), which differs from 5-ASA only for the position of the amino group, might be a valid alternative. Therefore, 4-ASA at 2 g dosage, administered as rectal enema, was compared to an equivalent preparation of 5-ASA. We carried out a double-blind therapeutical trial, in which 63 patients, similarly matched for age, sex and extent of disease, took part. The analysis of the final results showed that in the 5-ASA group, 26 (81%) out of 32 patients improved clinically, 25 (78%) sigmoidoscopically and 15 (46%) histologically. In the group of the 31 patients treated with 4-ASA, 24 (77%) improved clinically, 24 (77%) sigmoidoscopically and 13 (41%) histologically. Since no difference was registered between the two types of treatment (p = 0.141, X2 test), 4-ASA could be a possible form of treatment for active ulcerative colitis. To compare the efficacy and safety of mesalamine (5-ASA) suspension enema versus oral sulfasalazine (SAS) in patients with active mild to moderate distal ulcerative colitis.
                Thirty-seven patients were randomly assigned to treatment with either rectal mesalamine, 4 g at night, (n = 19) or oral sulfasalazine, 1 g four times a day, (n = 18) in a 6-wk, double-blind, double-dummy, parallel-group, multicenter study. Patients known to be refractory to SAS or 5-ASA preparations were excluded. Efficacy was assessed by a physician-rated Disease Activity Index (DAI), which included symptom evaluations and sigmoidoscopic findings, by physician-rated Clinical Global Improvement (CGI) scores, and by Patient Global Improvement (PGI) scores. Safety was assessed by adverse event reports, clinical laboratory tests, and physical examination. Results. Mean DAI scores indicated significant improvement from baseline in both treatment groups. CGI scores indicated that 94% of the 5-ASA patients were either "Very Much Improved" or "Much Improved" at wk 6 versus 77% of the SAS patients. PGI ratings showed more improvement in the 5-ASA treatment group than in the SAS group at wk 2 (p = 0.02) and at wk 4 (p = 0.04). Adverse events, primarily headache and nausea, occurred significantly more frequently (p = 0.02) in the SAS than in the 5-ASA group (83 vs 42%). Three patients were withdrawn from SAS treatment because of adverse events.
                Rectally administered 5-ASA is as effective as oral SAS in treatment of active distal ulcerative colitis but is associated with fewer and milder adverse events. Patients treated with 5-ASA reported improvement earlier than those treated with SAS. Rectally administered mesalazine (5-aminosalicylic acid) is a recognized therapy for distal ulcerative colitis. It is frequently applied as a liquid enema. However, there are reasons (acceptability to the patient, more uniform topical dispersion and effective adhesion) to prefer a foam-based enema.
                This study compared a foam enema (2 g mesalazine per day, Claversal Foam) with a standard liquid enema (4 g mesalazine per day, Salofalk enema).
                Patients with active distal ulcerative colitis, diagnosed according to standardized criteria, were treated for 4 weeks. The primary goal was clinical remission; endoscopic remission, histological changes, global assessment and standard safety measures were also analysed. A major subset of the patients also provided quality-of-life data.
                Both foam and liquid enema gave good rates of clinical and endoscopic remission. The foam enema was shown to be as efficacious as the reference, even though the daily dose in the foam treatment contained only half as much active drug as in the reference treatment. Minor regional differences in efficacy were seen. The tolerabilities of the two formulations were comparable.
                The foam enema offers a safe, efficacious and acceptable treatment for distal ulcerative colitis. Topical treatment is effective in patients with distal ulcerative colitis. This trial compares the efficacy, safety, and practicality of 4 weeks' treatment with 500 mg mesalazine suppositories with those of 178 mg hydrocortisone foam, both given twice daily.
                Seventy-nine patients with distal ulcerative colitis were stratified on the basis of the extent of the disease (proctitis and proctosigmoiditis) and randomized to one of the treatment groups. A disease activity index (DAI) based on symptoms and endoscopic findings was calculated. The patients evaluated the practicality of the treatment regimens, patients compliance was measured, and histologic findings recorded.
                Of all the patients 22% and 38% were complete responders after 2 and 4 weeks, respectively. Median DAIs in the mesalazine and hydrocortisone groups before and after 2 and 4 weeks' treatment were 14, 6, and 4, and 13, 8, and 6, respectively. The difference between the treatment groups was statistically significant (p = 0.02) due to a better effect of mesalazine in patients with proctitis. Patients' evaluation of practicality and patient compliance were statistically significantly better in the mesalazine group.
                Both treatment regimens are effective; mesalazine suppositories seem to be the preferred alternative. To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis (UC).
                In a multicenter investigator-blind trial, 375 patients with mild-to-moderate UC were randomized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk (W). Inclusion criteria were: disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index (CAI) 1-4 > or = 4. Primary end point was clinical remission at W4 defined as a CAI 1-4 < or = 2. Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5% unilateral confidence interval (97.5% CI) of the difference in remission rates between foam and liquid enema groups was greater than -15% .
                Remission rates at W4 in foam versus liquid were 68.3%versus 73.6% in per protocol (PP) population (lower limit of 97.5% CI -15.1%) and 66.7%versus 70.5% in intention-to-treat (ITT) population (97.5% CI -13.4%). Remission rates at W2 were 48.1 %versus 50.6% in ITT (97.5% CI -12.8%) and 49.1%versus 52.1% in PP (97.5% CI -13.8%) in foam versus liquid, respectively. Both treatments were well tolerated.
                A 4-wk treatment of 1 g mesalamine foam induced a clinical remission in 68% patients versus 73% with 1 g mesalamine liquid enema. Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis, it was achieved in the ITT population and at W2 in both populations. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis. 5-Aminosalicylic acid (5-ASA), the presumed active moiety of sulfasalazine, has shown clinical efficacy when administered per rectum as initial therapy to patients with distal ulcerative colitis. We report the results of a randomized double-blind trial comparing nightly retention of a 4-g 5-ASA enema with continued administration of hydrocortisone enemas in 18 patients with persistent active distal ulcerative colitis after at least a 3-wk course of treatment with 100-mg hydrocortisone enemas with or without oral sulfasalazine. Continuation of hydrocortisone enemas rather than placebo was used in the control group to reflect the realistic alternative therapy likely to be employed in current practice. Response to therapy was assessed after 3 wk by comparing pretreatment and posttreatment point scores of clinical, sigmoidoscopic, and histological severity. Improvement in clinical score was achieved in seven of nine 5-ASA enema-treated patients versus one of nine hydrocortisone enema-treated patients (p less than 0.05). Sigmoidoscopic and histological improvement generally paralleled clinical improvement. We conclude that in patients with distal ulcerative colitis unresponsive to standard therapy, treatment with 5-ASA enemas results in significant short-term clinical and sigmoidoscopic improvement in a majority of cases. Moreover, a significantly greater number of refractory patients improve when switched to 5-ASA enemas than when continued on standard therapy. To compare a low dosage (1 g/day) rectal preparation of 5-aminosalicylic acid in slightly acidic, buffered suspension (Pentasa) with a hydrocortisone 100 mg/day enema (Cortenema).
                Fifty-two patients with mild to moderate distal ulcerative colitis were randomized under double-blind conditions to receive a rectal preparation of either Pentasa (1 g/day) or Cortenema (100 mg/day) for 3 wk.
                After 3 wk, both types of treatment resulted in statistically significant improvements in clinical and endoscopic activity. No significant difference was observed between the two drugs in any of the parameters considered, although a statistical trend in favor of Pentasa was evident when analysis was limited to clinical activity (p = 0.07). No side effects were reported in either group.
                Our experience confirms that short term topical treatment with a low dosage 5-aminosalicylic acid is at least as effective as 100-mg hydrocortisone enemas in treating mild to moderate distal ulcerative colitis and is generally well tolerated. Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.
                To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.
                Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.
                A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.
                BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis. Budesonide is a new corticosteroid with high topical anti-inflammatory activity but little systemic effect. The aim of the present study was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5-ASA enema (mesalazine 1 g/100 mL) given for 4 weeks in the treatment of active distal ulcerative colitis and proctitis.
                Ninety-seven patients were studied in a multicentre single-blind randomized group-comparative trial. The primary efficacy variables were endoscopy and histopathology scores obtained at 0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables. Haematology, chemistry and adverse events were the safety variables.
                Budesonide and 5-ASA enemas both resulted in a significant improvement in endoscopy and histopathology scores but no difference could be demonstrated between the two treatment groups. There was also a significant improvement of symptoms (number of bowel movements per day, quality of stools, presence of blood and mucus, and state of well-being) within both groups but no difference between the two treatment groups. The clinical remission rate at 4 weeks was, however, 38% for patients treated with budesonide enema but 60% for those treated with 5-ASA enema (P = 0.03). No adverse events attributed to the study drugs were recorded in either of the groups.
                Budesonide enema 2 mg/100 mL appears to be as efficient and well-tolerated as 5-ASA enema in the treatment of active distal ulcerative colitis and proctitis. 5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis. Thirty-four patients with ulcerative colitis completed a double-blind assessment comparing the efficacy of two weeks of treatment with nightly retention enemas containing 3 g sulphasalazine or placebo. Symptom grading, sigmoidoscopic appearance, rectal biopsy specimens, and diary records were used to assess benefit and side effects. The active drug conferred significant benefit compared with placebo as shown by several criteria, but this benefit was confined to patients not already taking sulphasalazine by mouth. Overall assessment showed improvement in 11 of the 16 patients (70%) given the active treatment but in only two of the 18 (11%) given placebo. No side effects attributable to the drug were observed, even in patients previously intolerant to oral preparations. The logical therapeutic role of sulphasalazine enemas in ulcerative colitis would appear to be in patients who experience side effects such as nausea, abdominal discomfort, or headaches when taking the drug by mouth. Twenty-nine patients with attacks of distal ulcerative colitis were treated randomly with 3 g 5-aminosalicylic acid (5-ASA) or 30 mg of prednisolone phosphate sodium (PP) enemas (40 ml). Endoscopic, clinical, and histologic improvement were comparable in the two treatment groups. Our study showed that topical treatment with 5-ASA is as efficacious as PP in improving distal ulcerative colitis. The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis.
                Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit.
                At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated.
                The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone. nan Rectally administered mesalazine (mesalamine; 5-aminosalicylic acid) is the first-line therapy for treatment of distal ulcerative colitis. Recently, a high-volume 5-aminosalicylic acid foam has been shown to be as effective and safe as standard 5-aminosalicylic acid enema.
                To study the efficacy and safety of a low-volume vs. a high-volume 5-aminosalicylic acid foam.
                In this investigator-blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index > or = 4] were randomized to receive 2 x 1 g/30 mL low-volume (n = 163) or 2 x 1 g/60 mL high-volume 5-aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI < or = 4) at the final/withdrawal visit (per-protocol).
                330 patients were evaluable for efficacy and safety by intention-to-treat, 290 for per-protocol analysis. Clinical remission rates at week 6 (per-protocol) were 77% on low-volume foam vs. 77% on high-volume foam (P = 0.00002 for non-inferiority). The low-volume foam was associated with a lower frequency of severe discomfort, pain and retention problems.
                Low-volume 5-aminosalicylic acid foam is as effective and safe as a high-volume 5-aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high-volume preparation. We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P < 0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI -7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living.(ABSTRACT TRUNCATED AT 250 WORDS) Rectal formulations of mesalazine are the treatment of choice in mildly to moderately active ulcerative colitis. A new foam formulation of mesalazine was developed to improve both drug delivery and patient acceptance.
                In this multicentre, randomized, double-blind, parallel-group study, 111 patients with mildly to moderately active proctitis, proctosigmoiditis, or left-sided ulcerative colitis received mesalazine foam enema or placebo enema (2 g mesalazine per day) for 6 weeks. Disease activity was monitored on the basis of the Clinical Activity Index, Endoscopic Index, Histological Index, and global efficacy assessment by the investigators. Safety assessments included the recording of adverse events, laboratory variables and vital signs.
                Clinical remission was more frequent in the mesalazine group than the placebo group (65% vs. 40%; P=0.0082), particularly in patients with mild disease and patients with proctosigmoiditis. The frequency of patients with an endoscopic remission was higher in the mesalazine group (57%) than in the placebo group (37%). Similarly, 59% of patients receiving mesalazine but only 41% of those receiving placebo showed an improved Histological Index. The foam enemas were generally well-tolerated, and no treatment-related changes on laboratory variables and vital signs were noted.
                Mesalazine foam enema was well-tolerated and was more effective than placebo in the treatment of patients with distal ulcerative colitis. Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis.
                To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis.
                A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points.
                No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine.
                Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect. Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis.
                To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3mg) enema and foam versus mesalazine (2g) enema and foam in mild-moderate distal ulcerative colitis.
                In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate.
                Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0), 4 (T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student's t-test or the Wilcoxon-Mann-Whitney test.
                Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6-0.8] versus mesalazine 79% [95% confidence interval 0.6-0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7-0.9] versus mesalazine 90% [95% confidence interval 0.7-1.0]; p=n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1-0.3] versus mesalazine 28% [95% confidence interval 0.1-0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2-0.5] versus mesalazine 52% [95% confidence interval 0.3-0.6]; p=n.s.). The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p<0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p<0.001 for all three groups; T8 versus T0: p<0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p<0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0-4 versus 3, range 0-12; p<0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0-9 versus 3.5, range 0-8; p=n.s.). The safety profile was favourable for all groups.
                Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis. A new mesalazine rectal gel preparation (without propellant gas) has been recently developed to improve topical treatment in distal ulcerative colitis.
                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.
                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.
                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).
                The new mesalazine gel enema is efficacious and significantly better tolerated than the mesalazine foam enema. The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis.
                A four-week, randomized, single-blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (< or = 15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n = 29) compared with 400 mg of mesalazine suppositories administered three times per day (n = 29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physician's assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports.
                There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P < 0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P < 0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups.
                Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis. Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed.
                Fifty patients with active ulcerative colitis extending not beyond 20 cm from the anus on sigmoidoscopy, participated in a randomized single-blind study comparing the efficacy, tolerance and acceptance of the new Pentasa mesalazine 1 g suppository, given once daily versus Claversal mesalazine 500 mg suppository b.d.
                After 2 weeks, clinical remission was observed in 16 of 25 (64%) in the Pentasa group and in 7 of 25 (28%) in the Claversal 500 mg b.d. treated group; sigmoidoscopic remission occurred in 13 of 25 (52%) in the Pentasa group and in six of 25 (24%) in the Claversal group (P < 0.01). After 4 weeks, clinical and sigmoidoscopic remission were observed, respectively, in 84 and 76% of patients treated with Pentasa suppositories, and in 80 and 72% of patients treated with Claversal suppositories 500 mg b.d. (P = N.S.). The patients' evaluation for tolerability and practicality showed that the Pentasa suppository was significantly superior to the Claversal suppository.
                Pentasa 1 g suppository once daily induces a quicker clinical and sigmoidoscopic remission, and was better tolerated, than the Claversal 500 mg suppository b.d., and it may represent an advance for the topical treatment of distal proctosigmoiditis. Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA.
                Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index < or =4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions.
                Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, -12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease.
                Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis. Mesalazine enemas are of well proven efficacy for the topical treatment of distal ulcerative colitis. Although new rectal formulations of mesalazine are not expected to be superior in efficacy and tolerability to standard formulations, they may offer secondary advantages in terms of overall acceptability.
                To compare the efficacy, tolerability and overall acceptability of a new mesalazine rectal foam (Salofalk foam) with mesalazine enema in the treatment of active distal ulcerative colitis.
                A multicentre study was carried out in patients with active proctitis, proctosigmoiditis and left-sided ulcerative colitis as evaluated by the Clinical Activity Index (CAI > or =4) and Endoscopic Index (EI > or =6). Patients were randomly assigned to receive, in open-label fashion, either mesalazine foam 2 g twice a day or mesalazine enema (2 g/60 ml twice a day) for 3 weeks. Patients who did not achieve remission (defined as CAI <4 and EI <6) after 3 weeks continued the study receiving the alternative galenic formulation for a further 3 weeks.
                A total of 195 patients were enrolled. Characteristics at baseline were similar except for concomitant therapy with oral 5-ASA products: during the 1st treatment phase, 41% of patients on enema received such treatment vs only 29% of those on foam. Patients with at least one post-treatment efficacy evaluation were included in the intent-to-treat analysis (n=89 foam, n=96 enema). After 3 weeks of treatment, 112 patients were in remission and only 59 patients entered the 2nd treatment phase thus providing data on acceptability. Remission was achieved after 3 weeks in 54% of patients treated with foam and in 67% of those treated with enema. The 90% confidence interval for the difference in remission rates was 0 to 24 and thus within the clinically acceptable range of therapeutic equivalence. At the end of the 2nd phase, 70% of patients switched to foam were in remission vs 65% to the enema. Two patients discontinued treatment with foam prematurely due to anal burning. No clinically important changes were seen in the laboratory tests.
                Salofalk foam and enema are equally effective for the treatment of proctitis, proctosigmoiditis and left-sided ulcerative colitis. The new foam preparation is as well tolerated and accepted as enemas and can be used as a therapeutic alternative to conventional mesalazine enema formulations. Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated. Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given 99mTc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis. Sixty patients with active distal ulcerative colitis participated in a multicentre randomized double-blind trial to compare the effect of a beclomethasone dipropionate (BDP) enema (3 mg/100 ml) with 5-aminosalicylic acid (5-ASA) enemas (2 g/ 100 ml) and enemas with a combination of BDP/5-ASA (3 mg/2 g/100 ml). The patients were treated for 4 weeks and the efficacy of the drugs was evaluated by sigmoidoscopy, histology and subjective symptoms after that time. The overall results after 28 days of treatment were: clinical improvement 100% (BDP/5-ASA) vs. 70% (BDP) and 76% (5-ASA); endoscopic improvement 100% (BDP/5-ASA) vs. 75% (BDP) and 71% (5-ASA); histological improvement 95% (BDP/5-ASA) vs. 50% (BDP) and 48% (5-ASA). After 4 weeks of treatment seven of 19 patients (37%) receiving BDP/5-ASA had healed endoscopically, compared with six of 20 receiving BDP (30%) and two of 21 receiving 5-ASA (10%). Two patients on 5-ASA and three on BDP had a marked deterioration during treatment. The combination of BDP and 5-ASA was significantly superior to single-agent therapy in terms of both improved sigmoidoscopic and improved histological score. No differences in improvement between the 5-ASA vs. BDP-treated patients were noticed. No side effects were seen. The results of the study show that topical treatment of active distal ulcerative colitis with either 5-ASA or BDP is equally efficacious. So far, no data on topical combination therapy have been described. However, combination therapy with BDP/5-ASA seems superior to single-agent therapy and causes no adverse reactions. A multicentre double-blind study was conducted to evaluate the efficacy and tolerability of 1 g or 1.5 g mesalazine daily compared with placebo in 94 patients with mild to moderate distal proctosigmoiditis (less than 20 cm). The study end point was the determination of clinical, endoscopic, and histologic remission rates at 4 weeks. Eleven patients, nine receiving placebo and two receiving 1.5 g mesalazine, withdrew during trial, mostly because of worsening of symptoms. At 4 weeks clinical remission was achieved in 7 of 31 (39%) patients with placebo, in 22 of 32 (69%) patients in the 1 g mesalazine group, and 23 of 31 (74%) patients in the 1.5 g mesalazine group. No serious clinical or biochemical side effect of treatment was reported. Mesalazine suppositories are safe, well tolerated, and very effective in patients with active distal proctosigmoiditis: 500 mg twice daily appears a suitable dose regimen. Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.